[b cell chronic lymphocytic leukemia, cll, important, most, prognosis]- B cell chronic lymphocytic leukemia ( CLL) is a disease of expanding monoclonal B cells whose B cell receptor (BCR) mutational status defines 2 subgroups; patients with mutated BCRs have a more favorable prognosis than those with unmutated BCRs. CLL B cells express a restricted BCR repertoire including antibodies with quasi-identical complementarity-determining region 3 (CDR3), which suggests specific antigen recognition. The antigens recognized by CLL antibodies may include autoantigens since about half of CLL B cells produce autoreactive antibodies. However, the distribution of autoreactive antibodies between Ig heavy-chain variable-unmutated (IgV-unmutated) CLL (UM-CLL) and IgV-mutated CLL (M-CLL) is unknown. To determine the role of antibody reactivity and the impact of somatic hypermutation (SHM) on CLL antibody specificity, we cloned and expressed in vitro recombinant antibodies from M- and UM-CLL B cells and tested their reactivity by ELISA. We found that UM-CLL B cells expressed highly polyreactive antibodies whereas most M-CLL B cells did not. When mutated nonautoreactive CLL antibody sequences were reverted in vitro to their germline counterparts, they encoded polyreactive and autoreactive antibodies. We concluded that both UM-CLLs and M-CLLs originate from self-reactive B cell precursors and that SHM plays an important role in the development of the disease by altering original BCR autoreactivity..[Maxime:2005]{Human}
[b cell chronic lymphocytic leukemia, cll, lymphocytes, lymphocyte]- To define further the role of marrow T suppressor lymphocytes in the pathogenesis of the hypoproliferative anemia in all Rai clinical stages of B cell chronic lymphocytic leukemia ( CLL), marrow erythroid progenitor cell (CFU-E and BFU-E) frequency, marrow T gamma lymphocyte frequency per 1,000 nucleated marrow cells, and T cell-erythroid progenitor cell interactions were examined in 30 CLL patients and normal control subjects..[Mangan:1985]{Human}
[blood lymphocyte, chronic lymphocytic leukemia, classified, cll]- Peripheral blood lymphocyte morphology and karyotype were correlated across the spectrum of cytogenetic abnormalities in 78 previously karyotyped cases of B-cell chronic lymphocytic leukemia ( CLL). Cases were classified according to French-American-British morphologic criteria as typical CLL or CLL, mixed-cell type; the latter category was divided into CLL with a mixture of small and large cells and CLL with increased prolymphocytes ( CLL/PL)..[Kroft:1997]{Human}
[chronic lymphocytic leukemia, cll, leukemias, most]- It has been reported that telomeres are shortened in acute leukemias where the cell turnover is high. B-cell chronic lymphocytic leukemia ( CLL) is a particularly interesting haematological malignancy in regard to telomere dynamics because most of the malignant cells in CLL are mitotically inactive. In this study, we analysed the telomere length in patients with B-cell CLL in a comparison with the control group by using ddPRINS technique..[Sukru:2006]{Human}
[chronic lymphocytic leukemia, cll, most important, prognosis]- B-cell chronic lymphocytic leukemia ( CLL) is a clinically heterogeneous disease with many patients surviving for decades with minimal or no treatment, whereas others succumb rapidly to their disease despite therapy. In recent years, new molecular prognostic factors have emerged in CLL that have significantly improved the subgrouping of the disease. One of the most important molecular predictors, the immunoglobulin V(H) gene mutation status, divides CLL into two prognostic groups, depending on the presence or absence of somatic hypermutation, where unmutated V(H) genes are associated with considerably worse prognosis than mutated V(H) genes. An exception to this appears to be CLL patients utilizing the V(H)3-21 gene as they have poor outcome irrespective of mutation status..[Gerard:2005]{Human}
[b cell chronic lymphocytic leukemia, cll]- Following allogeneic stem cell transplantation (SCT), we studied the presence of donor and recipient derived cells within the CD19+ B cell fraction, in patients with B cell chronic lymphocytic leukemia ( CLL)..[Mattsson:2000]{Human}
- Eight previously treated and four untreated patients with B cell chronic lymphocytic leukemia ( CLL) received 20 X 10(6) U/m2 recombinant leukocyte interferon clone A (rIFN-alpha A) intramuscularly three times a week for 8 weeks..[Schulof:1985]{Human}
- B cell chronic lymphocytic leukemia ( CLL) is a malignancy of the CD5+ B cells..[Rassenti:1993]{Human}
[b cell chronic lymphocytic leukemia, inferior prognosis, most]- The most frequent chromosome aberrations in B cell chronic lymphocytic leukemia (B-CLL) detected by conventional chromosome banding analysis are trisomy 12 followed by structural abnormalities of the long arms of chromosomes 13, 14, and 11. Complex karyotypes, trisomy 12, and a '14q+' abnormality have been associated with inferior prognosis, whereas aberrations of 13q have been found in patients with a favorable outcome..[D?hner:1997]{Human}
[chronic lymphocytic leukemia, cll, important, lymphocyte]- These genes may be important in the development of nitrogen mustard (NM) drug resistance in B-cell chronic lymphocytic leukemia (B-CLL). Using Western blot analysis, we examined the levels of Bcl-2, Bax, Bcl-X and p53 protein expression and determined whether the levels of these proteins correlated with in vitro drug resistance in CLL patients' lymphocyte samples. Our investigations suggest that in CLL, NM drug resistance develops without any detectable alteration of Bcl-2, Bax or Bcl-X..[Christodoulopoulos:1998]{Human}
[chronic lymphocytic leukemia, cll, important, most]- This well-documented acquired anomaly is one of the most specific numerical chromosome alterations to occur in human hematological malignancies. We have cytogenetically characterized bone marrow and peripheral blood cells from a patient with B-cell chronic lymphocytic leukemia ( CLL) having a unique acquired translocation involving chromosomes 6 and 12, t(6;12) (p21.3;q13), which implicates band 12q13 as the site of the gene(s) important in this lymphoproliferative B-cell disorder. Aneuploidy, in the form of trisomy of chromosome 12, is not a requirement for neoplastic transformation in B-cell CLL, but gene rearrangement (present case) or nondisjunctional acquisition of additional copies of defective genes on chromosome 12 at band q13 may be involved in the genesis or progression of this disorder..[Stock:1999]{Human}
[chronic lymphocytic leukemia, cll, prognosis]- Therapeutic options are limited and the prognosis is poor for patients with fludarabine-refractory B-cell chronic lymphocytic leukemia ( CLL). Bortezomib induces apoptosis in vitro in CLL cells, both alone and in combination, including in cells resistant to fludarabine or other agents. The aim of the current randomized, open-label, Phase II study was to investigate the clinical activity of bortezomib in patients with fludarabine-refractory B-cell CLL..[Stefan:2006]{Human}
- Fifty-three patients affected with B-cell chronic lymphocytic leukemia ( CLL) younger than 50 years and observed in two hematological institutions have been retrospectively evaluated in order to verify whether this disease has different clinico-hematological features at presentation and different prognosis as compared to older cases. In our experience young cases with B-CLL diagnosis, confirmed by immunophenotype in 90.5% of patients, accounted for 7.1% of the whole CLL population..[Molica:1994]{Human}
[chronic lymphocytic leukemia, cll, lymphocytes]- Trisomy of chromosome 12 is one of the commonest cytogenetic abnormalities in the karyotype in chronic lymphocytic leukemia ( CLL). It is associated with atypical morphology of lymphocytes, progressing disease and poor survival. A high incidence abnormality in the B-cell CLL is deletion of chromosome 13 (13q14) detected by using modern diagnostic methods such as southern blot hybridization and fluorescence in situ hybridization. It occurs in 51% of the CLL patients and in as much as 70% in mantle-cell lymphoma..[Karnolsky:2001]{Human}
- T-lymphocyte colony formation in agar culture was investigated in 20 untreated B-cell Chronic Lymphocytic Leukemia ( CLL) patients in stage O. As compared to the controls, colony growth was very poor when unseparated peripheral-blood lymphocytes from CLL-patients were seeded. The number of colonies was greatly higher when T-cell enriched fractions from CLL were plated; however, they failed to reach the normal range even in this experimental condition..[Neri:1982]{Human}
[b cell chronic lymphocytic leukemia, b cell leukemia]- B cell chronic lymphocytic leukemia (B-CLL) is a common clonal B cell leukemia that is often accompanied by a multitude of immune abnormalities..[Bartik:1998]{Human}
[chronic lymphocytic leukemia, cll, lymphocyte]- Soluble CD23 (sCD23) and beta-2 microglobulin (beta2-m) are reliable prognostic parameters in B-cell chronic lymphocytic leukemia ( CLL); however, their merit over well-established clinical variables such as clinical stages, bone marrow (BM) histology and lymphocyte doubling time (LDT) remains to be defined..[Molica:1999]{Human}
- CD5+, CD23+) B-cell chronic lymphocytic leukemia ( CLL). Although changes of CD20 antigen density did not correlate with clinical parameters representative of either tumor mass (i.e. clinical stage, histological pattern of bone marrow involvement, absolute peripheral blood lymphocytosis) or disease progression (i.e. lymphocyte doubling time), a trend toward a better life-expectancy was observed in the low CD20 expression group compared with the high CD20 expression group (p = 0.05; relative risk of death, 0.51, 95% confidence interval, 0.24-1.04)..[Molica:1998]{Human}
[chronic lymphocytic leukemia, classified, cll]- B-cell chronic lymphocytic leukemia ( CLL) can be classified as typical or atypical based on morphologic and immunophenotypic features..[O'Connor:2000]{Human}
[b cell chronic lymphocytic leukemia, classified, lymphocytes]- Seventy-six consecutive untreated patients with B cell chronic lymphocytic leukemia (B-CLL) and classified according to Binet's staging system were studied at the clinical presentation. Several immunologic parameters (number of total and T circulating lymphocytes and their surface membrane immunoglobulin [Smlg] phenotypes and levels of serum Ig) were evaluated with the aim of identifying a biologic marker of prognostic relevance..[Baldini:1985]{Human}
[b cell chronic lymphocytic leukemia, prognosis]- The use of telomere length and telomerase expression as new biological markers in cancer patients requires their correlation with disease prognosis. We, therefore, correlated the mean telomere length based on a telomere restriction fragment assay and the activity of telomerase measured with a telomeric repeat amplification protocol with clinical data and overall survival in 58 patients with B cell chronic lymphocytic leukemia (B-CLL)..[Bechter:1998]{Human}
[b cell chronic lymphocytic leukemia, class]- We previously demonstrated that treatment of B cell chronic lymphocytic leukemia (B-CLL) cells with one class of IS ODN, CpG ODN, alters their phenotype and increases their immunogenicity..[Bernd:2005]{Human}
[b cell chronic lymphocytic leukemia, lymphocyte]- For many decades, B cell chronic lymphocytic leukemia (B-CLL) stood out as a B cell-derived malignancy that was difficult to position within the framework of the available B cell differentiation scheme: First, the histology as well as the immunophenotype did not quite resemble that of any normal lymphocyte; second, in contrast to almost all other B cell tumor subtypes, the immunoglobulin variable region (IgV) genes of B-CLL cases could be either unmutated or somatically mutated; third, the genomic lesions observed in B-CLL were markedly distinct from those of the other major B cell malignancies, which typically exhibit balanced chromosome translocations..[Klein:2005]{Human}
[chronic leukemias/leukemia/leukemias, chronic lymphocytic leukemia, most, prognosis]- A role for ATM in the development of sporadic T-cell chronic leukemias is supported by the finding of loss of heterozygosity at 11q22-23 and ATM mutations in leukemias carrying TCL-1 rearrangements. Approximately 14% of B-cell chronic lymphocytic leukemia (B-CLL), the most common adult leukemia, carry deletions of the long arm of chromosome 11 at 11q22-23. Loss of heterozygosity at 11q22-23 and, more recently, absence of ATM protein, have been associated with poor prognosis in B-CLL..[Bullrich:1999]{Human}
[b cell chronic lymphocytic leukemia]- To clarify the cell cycle duration of stimulated cells in B cell chronic lymphocytic leukemia (B-CLL), sister chromatid differentiation (SCD) methodology was utilized..[Sadamori:1984]{Human}
- For B cell chronic lymphocytic leukemia (B-CLL) conflicting data have been reported regarding the incidence and prognostic significance of 6q deletions..[Stilgenbauer:1999]{Human}
[chronic lymphocytic leukemia/leukemia, cll, important, lymphocytes, lymphocyte, most, prognosis]- Recent reports of successfully completed cytogenetic studies using polyclonal B-cell activators demonstrate that trisomy-12 and 14 q+ are the most frequently observed chromosomal abnormalities in B-cell chronic lymphocytic leukemia ( CLL). It appears that when trisomy-12 is accompanied by yet another abnormality, the prognosis of patients is uniformly poor. Patients in early stages of CLL retain delayed hypersensitivity reactivity, while those in advanced stages are usually anergic. The lymphocytes from venous blood of patients with CLL appear to retain at least some ability to respond to stimulation with mitogens in early stages, whereas in advanced stages they show no response to mitogens. Serum immunoglobulin levels are normal in the early (0 and I) stages, are markedly decreased in the advanced (III and IV) stages, and are somewhat between these extremes in the intermediate (II) stage of CLL. Prolymphocytic leukemia and prolymphocytoid transformation of CLL are indicators of poor prognosis, while a morphological variant characterized by large granular lymphocyte is associated with good prognosis. At this time it is not possible to ascribe strong prognostic significance to phenotypic features of lymphocytes in B-CLL; however, studies currently in progress may soon provide important insights on this subject..[Rai:1987]{Human}
[blood lymphocyte, chronic lymphocytic leukemia]- We performed a feasibility study systematically comparing large-scale gene expression profiles with clinical features in human B-cell chronic lymphocytic leukemia (B-CLL). cDNA microarrays were employed to determine the expression levels of 1,024 selected genes in 54 peripheral blood lymphocyte samples obtained from patients with B-CLL..[Stratowa:2001]{Human}
[chronic lymphocytic leukemia, prognosis, inferior]- ZAP-70 and CD38 expression can identify B-cell chronic lymphocytic leukemia with an inferior clinical outcome. Many groups have investigated the meaning of the expression of these two proteins and the correlation with the bad prognosis in B-CLL..[Nicolas:2007]{Human}
[chronic lymphocytic leukemia, lymphocytes, most]- A 70-year-old woman was diagnosed with B-cell-type chronic lymphocytic leukemia (B-CLL) in May 2001. Initial white blood cell (WBC) count was 37 x 10(9)/l and most of the cells were mature small lymphocytes..[Naoko:2005]{Human}
[chronic lymphocytic leukemia, prognosis]- The goal of this study was to evaluate the relation of chromosomal abnormalities detected by fluorescence in situ hybridization (FISH) in the prognosis of B-cell chronic lymphocytic leukemia (B-CLL) patients..[Beyhan:2008]{Human}
- The usage of the immunoglobulin (Ig) V(H)3-21 gene is associated with poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) despite V(H) gene mutation status..[Susann:2005]{Human}
- In B-cell chronic lymphocytic leukemia (B-CLL) the Rai and Binet staging criteria are not always able to accurately predict the prognosis of each patient..[Boonstra:2005]{Human}
- Chromosomal abnormalities in B-cell chronic lymphocytic leukemia (B-CLL) have been shown to correlate with prognosis..[Jahrsd?rfer:2005]{Human}
[b cell chronic lymphocytic leukemia/leukemia, b cell cll, cll]- We studied a variant CD5- B cell chronic lymphocytic leukemia ( CLL) cell population that produces pathologic IgM kappa rheumatoid factor autoantibodies. In contrast to common CD5+ B cell CLL, this variant leukemia cell population displays intraclonal diversity in its expressed Ig V genes, similar to that noted for follicular B cell non-Hodgkin's lymphomas. Also, in contrast to common B cell CLL, these leukemia cells rapidly undergo cell death hours after being placed in tissue culture..[Kobayashi:1994]{Human}
[chronic lymphocytic leukemia/leukemia, cll, leukemias, lymphocytes]- B-cell chronic lymphocytic leukemia ( CLL) is a highly common form of leukemia characterized by the accumulation of long-lived, functionally inactive, mature appearing neoplastic B lymphocytes. In addition, immune disturbances such as hypogammaglobulinemia and autoimmune phenomena (particularly, autoimmune hemolytic anemia) are frequently found in CLL patients [1-2]. The etiology of CLL is unknown. In contrast with other leukemias, there is no relationship between CLL and exposure to radiation or other cytotoxic agents. A genetic basis is highly likely since there are differences in the incidence of CLL in different countries (e.g., CLL accounts for 30%-40% of all the leukemias in Western countries as compared to 5%-10% in Asian countries) and the risk of contracting CLL is higher among persons with first-degree relatives with the disease [3]. Because the incidence of CLL increases with age and the longer life expectancy of the general population, the age of patients at diagnosis is increasing..[Montserrat:1997]{Human}
[b cell cll/lymphocytic leukemia, cll, leukemia]- However, a recent report indicated that VH251, one of three VH genes belonging to the VH5 subgroup (e.g., VH251, VH32, and VH15), not only is frequently rearranged in this disease, but also has extensive and selective mutations when expressed by CLL B cells. The extent and nature of these mutations contrasts markedly from the low level of mutations noted in VH5 genes used by normal B cells or other Ig V genes found expressed in CLL. To determine whether this difference reflects a unique property of VH251 or a previously unrecognized subgroup of CLL, we examined for VH5 Ig gene rearrangements in leukemia cells from 68 patients that satisfied clinical and diagnostic criteria for CD5+ B cell CLL. Southern blot hybridization studies with probes for VH251 and the JH locus revealed that only 7 (10%) of the 68 monoclonal CLL cell populations had undergone Ig gene rearrangement involving VH5 genes. Two (3%) were found to have functionally rearranged VH5 genes that shared > or = 98% sequence homology with 5-2R1, a VH251 gene isolated from a pre-B cell acute lymphocytic leukemia. The other five CLL (7%) had functionally rearranged VH5 genes that each shared > or = 99% nucleic acid sequence homology with a germline VH32 isolated from human sperm DNA..[Rassenti:1993]{Human}
[chronic lymphocytic leukemia, important]- Soluble CD23 (sCD23) was proposed as a marker of disease activity and as an important prognostic parameter in B-cell chronic lymphocytic leukemia (B-CLL)..[Saka:2006]{Human}
[chronic lymphocytic leukemia, lymphocyte]- A large number of prognostic factors are available to help predict the outcome of patients who present with B-cell chronic lymphocytic leukemia (B-CLL). These include clinical stage, leukemic cell morphology, lymphocyte doubling time, the pattern of infiltration in bone marrow trephine biopsies, cytogenetic abnormalities, p53 function and serum factors such as beta-2 microglobulin..[Tryfonia:2004]{Human}
[cll, chronic lymphocytic leukemia/leukemia, lymphocytic]- Granulomatous cutaneous reactions are well described in association with T-cell non-Hodgkin lymphoma and Hodgkin lymphoma, but are rarely seen in association with B-cell non-Hodgkin lymphoma or leukemia. We report a case of a 65-year-old woman with B-cell chronic lymphocytic leukemia ( CLL)/small lymphocytic lymphoma (SLL) who presented with multiple, tender, firm pink papules on the face, upper trunk and upper extremities 6 years after diagnosis of CLL. Biopsy revealed both palisading granulomatous dermatitis consistent with actinic granuloma and a dense perivascular lymphocytic infiltrate consistent with the patient's known history of leukemia. This is an unusual manifestation of cutaneous B-cell CLL that is rarely seen..[Julia:2012]
[cll, chronic lymphocytic leukemia/leukemia, lymph]- We investigated the effects of stromal cells, obtained from lymph nodes with various lymphoid disorders and characterized immunocytochemically as fibroblasts, on the maturation of a cell line "HN" established from an atypical PLL (prolymphocytic leukemia) having phenotypic characteristics of both CLL ( chronic lymphocytic leukemia) and HCL (hairy cell leukemia). Coculture with stromal cells, irrespective of the kind of lymphoid disease affecting the lymph node, induced a plasmacytoid cytology in HN cells, an increase of cIg gamma, and decreases of sIg gamma, CD5, CD21, HC2, and B-ly7..[Takeuchi:1995]{Human}
[cll, chronic lymphocytic leukemia/leukemia, prognoses]- Strong evidence exists for an association between high vascular endothelial growth factor (VEGF) levels and poor prognoses in patients with solid tumors and acute leukemia. Using Western blot analysis and solid-phase radioimmunoassay, we measured cellular VEGF levels in B-cell chronic lymphocytic leukemia ( CLL) samples from 225 patients and correlated these levels with disease characteristics and prognoses. The median VEGF level in CLL samples was 7.26 times the median level detected in normal peripheral blood mononuclear cells..[Aguayo:2000]{Human}
[chronic lymphocytic leukemias/leukemia, cll, lymphocytes]- The expression of a series of adhesion receptors: L-selectins (CD62L): Leu-8, several integrins (LFA-1: CD11a/CD18, VLA-4: CD49d/CD29 and VLA-5: CD49e/CD29), ICAM-1(CD54) and the 'homing receptor' (CD44) were investigated by a dual color flow cytometry in 56 cases of B cell disorders namely, 39 chronic lymphocytic leukemias ( CLL), four hairy cell leukemia (HCL), seven splenic lymphoma with villous lymphocytes (SLVL) and six other non-Hodgkin's lymphoma (NHL)..[Csanaky:1997]{Human}
[cll, leukemia, lymphocytes]- The surface phenotype of these cells was identical to that of circulating lymphocytes, indicating meningeal involvement of leukemia, a rare complication in B-CLL. At the time of this WBC elevation, 24% of circulating lymphocytes had prominent nucleoli, indicating progression of the disease to CLL/prolymphocytic leukemia..[Naoko:2005]{Human}
[cll, lymph, most]- CLL cells were cleared from blood in 95% patients in a median time of 21 days. CR or nodular PR in the bone marrow was achieved in 66% of the patients and most patients achieved this after 18 weeks of treatment. An 87% OR (29% CR) was achieved in the lymph nodes..[Jeanette:2002]{Human}
[chronic lymphocytic leukemia/leukemia, cll, most]- B-cell chronic lymphocytic leukemia ( CLL) is the most common human leukemia. Deregulation of the T-cell leukemia/lymphoma 1 oncogene (TCL1) in mouse B cells causes a CD5(+) leukemia similar to aggressive human CLL..[Alexey:2012]
[cll, b cell chronic lymphocytic leukemia/leukemia, most]- The most common human leukemia is B cell chronic lymphocytic leukemia ( CLL), a malignancy of mature B cells with a characteristic clinical presentation but a variable clinical course. The rearranged immunoglobulin (Ig) genes of CLL cells may be either germ-line in sequence or somatically mutated. Lack of Ig mutations defined a distinctly worse prognostic group of CLL patients raising the possibility that CLL comprises two distinct diseases. Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression "signature," irrespective of Ig mutational status, suggesting that CLL cases share a common mechanism of transformation and/or cell of origin..[Rosenwald:2001]{Human}
[chronic, cll/cll lymphocytes, important, lymphocytes]- In this report, we have examined the expression and distribution of HsRad51 protein in lymphocytes from patients with B-CLL to see whether the expression of HsRad51 is associated with NM damage to the malignant B lymphocytes, specifically chlorambucil (CLB), which is the standard alkylating agent used to treat patients with B-CLL. We have analyzed the intracellular distribution of HsRad51 protein in these lymphocytes before and after treatment with CLB by immunofluorescence. In vitro CLB treatment induces Rad51 expression, as measured by increased immunopositive staining in all CLL samples. In the CLB-resistant CLL lymphocytes, there was a linear correlation between induction of Rad51 protein at 5.4 microM CLB and the in vitro LD50 dose of CLB. Surprisingly, although it has been reported that Rad51 is induced in S phase and only 10% of cells from cell lines expressed positive immunostaining for Rad51, our CLL lymphocytes, which were not subjected to in vitro drug exposure, were 90% positive for Rad51, despite their nonproliferative state, which suggests that there is chronic activation of the protein. Our results suggest that CLB activates HsRad51-directed recombination repair and that this process may be important in NM drug-induced cytotoxicity..[Christodoulopoulos:1999]{Human}
[chronic lymphocytic leukemia, cll]- To establish xenograft models of human B-cell chronic lymphocytic leukemia ( CLL), we inoculated 5 x 10(6) D10-1 cells, a subline of Epstein-Barr virus (EBV)-transformed human B-cell CLL with a marker chromosomal anomaly, into SCID or irradiated nude mice by the intravenous (i.v.) or intraperitoneal (i.p.) route..[Zhu:1994]{Human}
- Mutations of exons 5 to 8 of the p53 gene were looked for in 39 cases of B-cell chronic lymphocytic leukemia ( CLL) using polymerase chain reaction single-strand conformation polymorphism analysis and DNA sequencing..[Fenaux:1992]{Human}
- In order to obtain more information on the pattern of CD11c-positivity in otherwise typical B-cell chronic lymphocytic leukemia ( CLL), we analyzed immunological and clinico-pathological features of 99 such patients studied with two different monoclonal antibodies (MoAbs)..[Molica:1995]{Human}
- The genetic features of B-cell chronic lymphocytic leukemia ( CLL) are currently being reassessed by molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH). Conventional cytogenetic studies by chromosome banding are difficult in CLL mainly because of the low in vitro mitotic activity of the tumor cells, which leads to poor quantity and quality of metaphase spreads. Molecular genetic analyses are limited because candidate genes are known for only a few chromosomal aberrations that are observed in CLL. FISH was found to be a powerful tool for the genetic analysis of CLL as it overcomes both the low mitotic activity of the CLL cells and the lack of suitable candidate genes for analysis..[Stilgenbauer:2001]{Human}
- After i.v. or i.p. inoculation of 5 x 10(6) D10-1 cells, a subclone of an Epstein-Barr virus transformed human B-cell chronic lymphocytic leukemia ( CLL) line, 100% of nude mice developed solid or ascites tumors and died within 17-60 days of tumor inoculation..[Zhu:1994]{Human}
- A 70-year-old woman with a 2-year history of B-cell chronic lymphocytic leukemia ( CLL) developed headache, fever, chills, and weakness..[Lee:1995]{Human}
- Blood mononuclear cells from 540 newly diagnosed, unselected patients with B-cell chronic lymphocytic leukemia ( CLL) were examined by immunofluorescence flow cytometry for a panel of surface membrane markers, including IgM and IgD, the monoclonal antibodies anti-CD3, -5, -20, -21, -22, -FMC7, and, for the final 125 patients, anti-CD23..[Geisler:1991]{Human}
- CD38 is a transmembrane glycoprotein expressed on the surface of leukemic cells in a significant percentage of patients with B-cell chronic lymphocytic leukemia (B-CLL). A recent study suggested that CD38 expression has prognostic value in CLL..[Ibrahim:2001]{Human}
[b cell cll, cll]- Treatment with rIFN-alpha A was associated with a depression of nonspecific and specific humoral immunity in assays employing cryopreserved autologous pretherapy CLL cells. No consistent effects were demonstrable in cytolytic assays with purified peripheral blood T cells as effector cells, including one that utilized autologous CLL target cells. rIFN-alpha A has limited antitumor activity in B cell CLL which is restricted to untreated patients with an early stage of disease..[Schulof:1985]{Human}
[b cell leukemia, cll]- There was no correlation between the expression of the adhesion molecules and clinical and laboratory parameters except for CD18 which was expressed on a significantly (P < 0.05) higher number of leukemic cells in CLL with more advanced stages. This study demonstrates that even closely related B cell leukemia/lymphomas have a certain well defined and strictly variable adhesion profile which is characteristic of the disease entity and therefore, the adhesion profile may offer additional information useful for differential diagnosis and study of disease pathogenesis..[Csanaky:1997]{Human}
[chronic lymphocytic leukemia/lymphocytic, cll]- B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma ( CLL/SLL) may involve the bone marrow in nodular, interstitial, diffuse, or mixed patterns. However, B-cell CLL/SLL associated with large reactive germinal centers (the so-called interfollicular pattern) involving the bone marrow is not reported. We describe 2 examples of B-cell CLL/SLL that subtotally replaced the bone marrow with an interfollicular pattern..[Kim:2000]{Human}
[chronic lymphocytic leukemia/chronic lymphocytic leukemias, lymphocytes, most]- Most B-cell chronic lymphocytic leukemias and a small normal subset of B lymphocytes express the T-cell-associated CD5 antigen; expression of other T-cell antigens has been reported only rarely. The authors report two cases of typical B-cell chronic lymphocytic leukemia, seen during 1 year, in which two-color flow cytometric analysis documented expression of the T-cell-associated CD8 antigen by the monoclonal B cells..[Koelliker:1994]{Human}
[classification, cll]- These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease..[Rosenwald:2001]{Human}
- Rai and Binet staging classifications and TTM score system retained their prognostic value in this CLL population. In addition, cases fulfilling criteria of "smoldering" CLL, had a very long survival (75% survival probability at 16 years)..[Molica:1994]{Human}
[cll, most important]- In parallel, the accurate evaluation of the incidence of chromosome aberrations in CLL by FISH allows the correlation of genetic abnormalities with clinical disease manifestations and outcome. In particular, 17p abnormalities and deletions in 11q22-q23 have already been shown to be among the most important independent prognostic factors identifying subgroups of patients with rapid disease progression and short survival..[Stilgenbauer:2001]{Human}
[cll, leukemia]- These findings contrast with a recently published study on VH5 gene expression in B CLL and contest the hypothesis that extensive somatic mutation is a common property of the VH5 genes used in this disease. Further work to define the clinical and/or phenotypic characteristics of patients with leukemia cells that express mutated versus nonmutated Ig V genes may reveal subsets of CLL that possibly differ in their cytogenesis, etiopathogenesis, and/or clinical behavior..[Rassenti:1993]{Human}
- Similarly, CLL samples with high Tcl1 expression showed a decrease in DNA methylation compared with CLL samples with low Tcl1 expression. Given the previous reports of inactivating mutations of DNMT3A in acute myelogenous leukemia and myelodysplastic syndrome, our results suggest that inhibition of de novo DNA methylation may be a common oncogenic mechanism in leukemogenesis..[Alexey:2012]
[chronic b cell leukemia, important, lymph]- We propose that lymph node stromal cells play an important role in the differentiation of B cells through direct contact and that HN cells will be useful for investigating the differentiation pathway of chronic B cell leukemia cells..[Takeuchi:1995]{Human}
[cll, prognosis]- The prognosis of patients with CLL is variable..[Montserrat:1997]{Human}
- Essential role in the pathogenesis of CLL is played by the aberrations in chromosome 17 and the p53 mutations (17p13.1). The gene p53 is defined as a tumour suppressor gene; mutations of this gene leads to a CLL characterized with rapid progression, aggressive course, poor prognosis and low survival..[Karnolsky:2001]{Human}
- In conclusion this study confirms that prognosis of young CLL patients can be easily assessed using the current well-defined criteria. Since age is not by itself a criterion for intensifying treatment, further efforts to identify those young CLL patients who qualify for more aggressive therapy should be made..[Molica:1994]{Human}
- Our data indicate that good prognosis cytogenetics correlates with less spontaneous apoptosis but greater in vitro immunogenicity. These findings could have significant implications on the design of future therapeutic approaches in patients with CLL, and the likelihood of response based on cytogenetics..[Jahrsd?rfer:2005]{Human}
[cll, prognoses]- However, in a subgroup of CLL patients with good prognoses or early-stage disease (Rai stages 0-II, Binet stages A,B; beta2-M </= 2.8 mg/dL), lower levels of VEGF were associated with shorter survival times..[Aguayo:2000]{Human}
[chronic lymphatic leukemia, chronic lymphocytic leukemia/leukemia]- The coexistence of acute myeloid leukemia and chronic lymphocytic leukemia in the same patient is rare. The majority of the cases correspond to patients that developed acute leukemia during the evolutionary course of a chronic lymphatic leukemia following treatment with chemotherapy drugs. We report a case of acute myelomonocytic leukemia concurrent with untreated B-cell chronic lymphocytic leukemia in which the use of flow cytometry analysis with a large panel of monoclonal antibodies, allowed the demonstration of different pathological populations and determine immunophenotyping patterns. Published cases of simultaneous chronic lymphocytic leukemia and acute leukemia are reviewed..[Viviana:2010]{Human}
[cll, important]- In this prospective study based on 106 B-cell CLL patients, we propose a combination of beta2-m and sCD23 as a strong prognostic system whose statistical significance was mainly due to an excess of deaths in the subgroup displaying increased serum levels of either beta2-m or sCD23. Multivariate survival analysis confirmed the important dominant role of such a finding, thus excluding features with a high degree of codependence (i.e. clinical stages, LDT) and including variables with low association (i.e..[Molica:1999]{Human}
[cll, most]- Using the interphase cytogenetic FISH approach with a disease specific set of probes, chromosome aberrations can be found in more than 80% of CLL cases. The most frequently observed abnormalities are losses of chromosomal material, with deletions in band 13q14 being the most common, followed by deletions in 11q22-q23, deletions in 17p13 and deletions in 6q21. The most common gains of chromosomal material are trisomies 12q, 8q and 3q. Translocation breakpoints, in particular involving the immunoglobulin heavy chain locus at 14q32, which are frequently observed in other types of non-Hodgkin's lymphoma, are rare events in CLL. Genes affected by common chromosome aberrations in CLL appear to be p53 in cases with 17p deletion and ataxia telangiectasia mutated (ATM), which is mutated in a subset of cases with 11q22-q23 aberrations..[Stilgenbauer:2001]{Human}
- Most samples from patients with CLL expressed the 43-kd VEGF isoform in addition to the commonly expressed 45-kd isoform..[Aguayo:2000]{Human}
- The percentage of leukemic cells expressing L-selectins (Leu-8) was high in CLL (52% of positive cases) and integrin expression (LFA-1, VLA-4, 5) was low (19 and 33%, respectively), while a reverse pattern, low Leu-8 (17%), and a high VLA-4 (77%), was observed in non-CLL cases. The expression of LFA-1 alpha-chain was variable in non-CLL cases, and the LFA-1 heterodimer was expressed on most clonal B cell in NHLs (92%)..[Csanaky:1997]{Human}
[chronic, important, lymphocytic leukemia]- The original observation that sera from patients with chronic B-cell lymphocytic leukemia (B-CLL) contain high amounts of soluble CD23 (sCD23), which reflect disease activity and tumor load has been confirmed by numerous reports and serial determinations of sCD23 are now recognized as important indicators of disease progression..[Schwarzmeier:2004]{Human}
[chronic lymphocytic leukemia/lymph, classification, important, prognosis]- B-cell chronic lymphocytic leukemia (B-CLL) is characterized by highly variable distribution of tumor mass between peripheral blood, bone marrow and lymphoid organs which is important for staging, classification and prognosis. These clinical findings with novel data about importance of B-cell receptor and its stimulation with the support of microenvironment indicate important role of tissues (lymphoid organs and bone marrow) in the pathogenesis of B-CLL. Here is presented the novel approach of simultaneous characterization of B-CLL cells form peripheral blood, bone marrow and lymph nodes by flow cytometry and immunocytochemistry, defining inter- and intraclonal diversity with respect to various molecules..[Ozren:2010]{Human}
[cll]- Immunoglobulin gene analysis has also indicated the possibility of antigen selection in CLL considering the significant bias in V(H) gene usage. Intriguingly, the V(H)3-21+ group and several other CLL subsets using certain V(H) genes was recently reported to display strikingly restricted immunoglobulin gene features, in both their heavy and light chain gene rearrangements, thus further high-lighting the possible role of antigen involvement in CLL development..[Gerard:2005]{Human}
- These results suggest that Dal B02 may be an effective carrier for the radioimmunotherapy of human B-cell CLL and other appropriate B-cell lymphomas, especially in the progressive phase of B-cell CLL, which is usually not amenable to currently available therapeutic modalities..[Zhu:1994]{Human}
- On the basis of the present experiments, it is suggested that the defective colony growth of T-cell fractions in B-cell CLL may be related to the low number of OKT4-positive cells plated, which are known to be mainly responsible for the colony generation in agar culture..[Neri:1982]{Human}
- Among the promising prognostic markers is flowcytometric analysis of CD38 on the monoclonal B cells in CLL..[Boonstra:2005]{Human}
- These results further support the concept of distinct CLL subgroups based on karyotype. Furthermore, the association of trisomy 12 and complex abnormalities with mixed-cell morphology may have implications for clonal evolution in CLL..[Kroft:1997]{Human}
- In the past two decades, significant progress has been made in CLL [4-10]. This review summarizes recent advances in the biology, diagnosis, and therapy of CLL..[Montserrat:1997]{Human}
- We used comparative genomic hybridization (CGH) to explore the cytogenetic relationship between typical and atypical B-cell CLL. Results showed a similar pattern of chromosome gains and losses detected in typical and atypical B-cell CLL, suggesting they are related disorders..[O'Connor:2000]{Human}
- We previously have shown the strong association between trisomy 12 as detected by FISH and CD11a expression in atypical B-cell CLL..[O'Connor:2000]{Human}
- We hypothesise that the telomeric erosion in CLL may reflect the dominance of malignant cells with an abnormally long life span..[Sukru:2006]{Human}
- The numbers of T gamma cells infiltrating CLL marrows were increased 3, 9, and 20 times normal in Rai O through II, Rai III through IV, and CLL-aplasia groups, respectively..[Mangan:1985]{Human}
- These findings suggest that p53 mutations are relatively rare in B-cell CLL, and largely predominate or may even be restricted to patients with 17p monosomy (who constitute about 5% of all B-cell CLL patients in large published series)..[Fenaux:1992]{Human}
- MDR1 was observed in 41% of CLL ZAP-70(+)CD38(+) and in 37% of CLL ZAP-70(-)CD38(-)..[Nicolas:2007]{Human}
- These findings suggest that the development of PRCA in B-cell CLL may result from suppression of CFU-E proliferation by T gamma cells..[Mangan:1983]{Human}
- Only one of six samples with acquired resistance to the nitrogen mustards had a p53 mutation suggesting that p53 mutations are not a prominent feature of acquired NM resistance in CLL..[Christodoulopoulos:1998]{Human}
- A remarkable finding was the detection of ICAM-1 in all CLL cases albeit the number of positive cells was significantly lower (P < 0.05) compared to non-CLL cases..[Csanaky:1997]{Human}
- As expected, the CLL was of B-cell lineage..[Lee:1995]{Human}
- Finally, on the basis combined increased serum levels of beta2-m and sCD23, a better stratification of low- and intermediate-risk patients could be obtained, thus allowing the formulation of a clinico-biological staging for CLL..[Molica:1999]{Human}
- Administration of 50 micrograms/mouse of Dal B02, an IgG1 (kappa) MAb directed against surface-associated antigens of human B-cell CLL, significantly prolonged the survival of D10-1-inoculated nude and SCID mice..[Zhu:1994]{Human}
- Although no objective responses were achieved in patients with fludarabine-refractory B-cell CLL, single-agent bortezomib demonstrated biologic activity..[Stefan:2006]{Human}
- Measurement of CD38 expression by flow cytometry should become a routine test in the evaluation of patients with CLL..[Ibrahim:2001]{Human}
- Our findings imply that shortened telomeres in CLL may be reflecting the "history" of the disease and serve as an independent prognostic factor..[Sukru:2006]{Human}
- Although variability of CD20 and Sm Ig expression make it possible to appreciate biological heterogeneity of B-cell CLL better, however, they cannot substitute well-established clinico-hematological features in the prognostic assessment of B-CLL patients..[Molica:1998]{Human}
- Although 3% to 5% of patients with B-cell CLL may develop higher-grade lymphoma, usually the lymphoma is of B-cell lineage and often represents a histologic manifestation of clonal evolution..[Lee:1995]{Human}
- Thus, besides clinical variables, CD23 and IgM intensity might be useful prognostic markers in the management of CD5+, B-cell CLL..[Geisler:1991]{Human}
- B-cell CLL/SLL may rarely involve the bone marrow with an interfollicular pattern..[Kim:2000]{Human}
[chronic/chronic lymphocytic leukemia, classification, leukemia/leukemias, most]- The classification of CD5-negative/CD10-negative chronic B-cell leukemias (CD5-/CD10- CBL) can be problematic. Most of these cases may represent leukemic non-Hodgkin's lymphoma (NHL) other than B-cell chronic lymphocytic leukemia (BCLL); nonetheless, some investigators still advocate the term "CD5-negative BCLL." Because adhesion molecule (AdMol) expression patterns reflect the biology of lymphoid neoplasms, we studied a series of 106 B-cell lymphoproliferative disorders, including CD5+ BCLL (n = 56), NHL other than BCLL (n = 35), and CD5-/CD10- CBL (excluding hairy cell leukemia and prolymphocytic leukemia) with no prior history of NHL (n = 15) for expression of components of the very late antigen-4 complex (alpha4/beta1 integrin (CD49d/CD29)), components of the mucosal addressin-cell adhesion molecule receptor (alpha4(CD49d)/beta7 integrin), and L-selectin (CD62L)..[Finn:2001]{Human}
[chronic/chronic lymphocytic leukemia/leukemia, leukemias, most]- Deletions or translocations of 13q, most commonly involving band 13q14, belong to the most frequent structural chromosome abnormalities in B-cell chronic lymphocytic leukemia (B-CLL). In a combined metaphase and interphase cytogenetic study using conventional G-banding analysis and fluorescence in situ hybridization (ISH) we previously analysed the retinoblastoma susceptibility gene (RB-1) and its chromosomal locus 13q14 in 35 patients with chronic B-cell leukemias. We report here on the interphase cytogenetic analysis of 109 cases with chronic B-cell leukemias [B-CLL = 90; B-prolymphocytic leukemia (B-PLL) = 6, hairy cell leukemia (HCL) = 13]; a subset of 49 patients (B-CLL = 45; B-PLL = 4) was studied by conventional G-banding analysis..[D?hner:1995]{Human}
[chronic lymphocytic leukemia/leukemia, leukemias]- By using a combination oligonucleotide probe hybridization and restriction enzyme polymorphism analysis, a series of 48 cases of B-cell chronic lymphocytic leukemia were investigated for activating point mutations at codons 12, 13 and 61 of the K-ras proto-oncogene. A small series of acute leukemias (seven with acute lymphoblastic leukemia (ALL), 11 with acute myeloid leukemia (AML)) were examined in parallel..[Browett:1988]{Human}
[chronic lymphocytic leukemia/leukemia, lymphocytes, most]- One of the main reasons for interest in these molecules is that they may play a determining role in neoplastic transformation and diffusion; in particular, in lymphoproliferative syndromes, a lack of cell adhesiveness or an abnormal adhesion pattern in neoplastic lymphocytes may free these cells from regulation, thus contributing towards the development of leukemia and/or lymphoma. Studies of VLA expression in B-cell leukemia/lymphomas show a modulation of VLA3 and VLA4 reactivity. The most interesting element is the identification of a VLA3/VLA4 pattern associated with B-cell chronic lymphocytic leukemia (B-CLL) characterised by a reduced expression of VLA4 and the constant expression of VLA3..[Baldini:1994]{Human}
[class, leukemia, most]- Moreover, we propose that the lack of chromosomal translocations in B-CLL may be related to their derivation from marginal zone B cells, since somatic hypermutation and Ig class switch, the processes that generate chromosome translocations in most germinal center (GC)-derived malignancies, are no longer active in marginal zone B cells. Also, we discuss similarities and differences between B-CLL and hairy cell leukemia (HCL) and suggest that also HCL may be derived from a post-GC memory or marginal zone B cell..[Klein:2005]{Human}
[chronic lymphocytic leukemia/leukemia, important, most]- B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in Western countries and results from the accumulation of B-lymphocytes which are functionally abnormal and predominantly non-cycling in vivo. Consequently, it is important to understand why B-CLL cells accumulate in GO phase. Since TGF-beta is an important negative regulator of the immune system, a loss of responsiveness to this factor might provide a selective advantage to B-CLL cells..[Lagneaux:1998]{Human}
[most important, prognosis]- Furthermore, based on the sensitive detection of chromosome abnormalities by FISH, more accurate correlations between chromosome abnormalities and prognosis can be performed. Deletion of the TP53 gene at 17p13 have already been shown to be one of the most important independent prognostic factors for survival..[D?hner:1997]{Human}
[lymphocyte, most, prognosis]- Most of these genes code either for cell adhesion molecules (L-selectin, integrin-beta2) or for factors inducing cell adhesion molecules (IL-1beta, IL-8, EGR1), suggesting that prognosis of this disease may be related to a defect in lymphocyte trafficking..[Stratowa:2001]{Human}
[chronic lymphocytic leukemia, lymphocytes]- The chromosome constitutions of stimulated lymphocytes in 21 untreated cases with B-cell chronic lymphocytic leukemia (B-CLL) were examined..[Sadamori:1984]{Human}
- In a prospective study, peripheral lymphocytes of 93 previously untreated patients with B-cell chronic lymphocytic leukemia (B-CLL) were evaluated with flow cytometry for the intensity of CD20 and surface immunoglobulin (sIg) light-chain (LC) expression..[Tefferi:1996]{Human}
- We have evaluated genomic aberrations by conventional cytogenetics and fluorescence in situ hybridization (FISH) analysis in a series of 57 Argentinean B-cell chronic lymphocytic leukemia (B-CLL) patients. The studies were performed on stimulated peripheral blood lymphocytes..[Christian:2003]{Human}
[b cell cll, lymphocytes]- We conclude that the hypoproliferative anemia occurring in the course of B cell CLL is due to gradual accumulation in the marrow of T gamma lymphocytes which suppress erythroid progenitor cell growth..[Mangan:1985]{Human}
[chronic lymphocytic leukemias/leukemia, lymphocytes]- One leiomyosarcoma and one extra-skeletal osteosarcoma showed a dCK levels comparable to those found in normal lymphocytes (84 +/- 6 and 109 +/- 4 ng/mg), while other sarcoma samples contained levels comparable to the gastrointestinal adenocarcinomas (20 +/- 7 ng/mg, n = 12). We confirm that dCK is expressed constitutively and predominantly in lymphoid cells, but conclude that a significant expression may be found in non-lymphoid tissues as well, with increased levels in the corresponding tumor tissue. 2-Chlorodeoxyadenosine (CdA), an antileukemic agent used in treatment of hairy cell leukemia and chronic lymphocytic leukemias (B-CLL), is phosphorylated by dCK which was used as the selective substrate for this enzyme..[Eriksson:1994]{Human}
[chronic/chronic leukemias/leukemia, chronic lymphocytic leukemia/lymphocytic leukemia/lymphocytic leukemias]- We determined the expression levels of the mdr1 and mdr3 multidrug-resistance genes (also known as PGY1 and PGY3, respectively) in peripheral blood cells from 69 adult patients with acute and chronic leukemias, using an RNase protection assay. Expression of mdr1 was found in samples from patients with acute nonlymphocytic leukemia (13 of 17), chronic myelocytic leukemia (CML, chronic phase, 10 of 10; blast crisis, three of four), acute lymphocytic leukemia (ALL, eight of 11), B-cell chronic lymphocytic leukemia (B-CLL, 17 of 17), hairy cell leukemia (HCL, one of two), and T-cell prolymphocytic leukemia (one of one), but not in B-cell prolymphocytic leukemia (B-PLL, 0 of seven). Expression of mdr3 was only detected in samples from B-cell lymphocytic leukemias: CML, lymphoid blast crisis (one of one), B-cell ALL (two of two), B-CLL (17 of 17), B-PLL (seven of seven), and HCL (two of two). In vitro drug uptake studies by on-line flow cytometry showed that in leukemia cells expressing either mdr1 or mdr3, the steady-state accumulation of daunorubicin could be significantly increased by addition of cyclosporine and, to a lesser extent, by verapamil. Because cyclosporine and verapamil are known as inhibitors of the mdr1-encoded P-glycoprotein drug-efflux pump, and because the mdr1 and mdr3 genes are highly homologous, our data suggest that the mdr3 gene encodes a functional drug pump in B-cell lymphocytic leukemias. The results of this study may have implications for clinical therapy for acute or chronic leukemias expressing the mdr1 or mdr3 gene, in particular, treatment with combinations of cytotoxic drugs plus agents that reverse multidrug resistance. Since mdr1 and mdr3 are frequently expressed in untreated as well as treated leukemia, such combination therapy should be considered for untreated patients as well as treated patients..[Herweijer:1990]{Human}
[important, lymph]- Multivariate analyses showed that CD38 expression is an important prognostic factor associated with high incidence of lymph node involvement (P =.004), lower hemoglobin level (P =.001), hepatomegaly (P =.05), and high beta2M level (P =.00005)..[Ibrahim:2001]{Human}
- The prognostic effect of 11q deletion on survival strongly depended on the age: in patients less than 55 years old, the median survival time was significantly shorter in the deletion group (64 months v 209 months; P < .001), whereas in patients > or = 55 years old there was no significant difference (94 months v 111 months; P = .82). 11q deletions identify a new clinical subset of B-CLL characterized by extensive lymph node involvement. In younger B-CLL patients, this aberration is an important predictor of survival..[D?hner:1997]{Human}
[important, prognosis]- Our data suggests that FISH analysis of B-CLL patients provides important diagnostic, clinical, and prognostic information which may help clinicians assess the prognosis and make appropriate treatment decisions..[Beyhan:2008]{Human}
- A number of interesting significant interactions have been discovered, pointing to the important role of neoplastic cell microenvironment. These may in addition to insights in pathogenesis and roles of different microenvironments add to diagnosis, prognosis and treatment of B-CLL patients..[Ozren:2010]{Human}
[lymph, most]- All the tumor-inoculated mice had histologically confirmed metastases in lymph nodes, and most of them also had metastases in one or more internal organs..[Zhu:1994]{Human}
[b cell leukemias/leukemia, most/most b cell cll]- Leukemia cell survival also could be enhanced by exogenous IFN-gamma or anti-CD40 presented on Fc gamma RII (CDw32)-expressing L cells, but not by exogenous IL-4, IL-6, or monomeric human IgG. We find that Ag acts directly on the leukemia B cells to inhibit apoptosis. This effect could be mimicked by cross-linking the leukemia cells' surface IgM receptors with immobilized murine mAb specific for human Ig mu-chains, but not by immobilized mAb of irrelevant specificity. In contrast to most follicular NHL, this leukemia B cell population does not have evidence of bcl-2 gene rearrangement. Also, in contrast to non-Hodgkin's lymphomas and most B cell CLL, these cells do not express detectable amounts of bcl-2. Finally, although capable of inhibiting apoptosis, surface Ig receptor cross-linking does not induce expression of bcl-2 in these variant leukemia cells. We hypothesize that the lack of bcl-2 expression may render these leukemia cells particularly dependent upon the survival signal(s) derived from surface Ig receptor cross-linking. This state may represent an early stage in leukemia/lymphomagenesis, possibly accounting for the intraclonal diversity observed in the Ig V genes expressed by certain CD5- B cell leukemias and lymphomas..[Kobayashi:1994]{Human}
[chronic lymphocytic leukemia/leukemia, most]- B-cell chronic lymphocytic leukemia (B-CLL) is the most common B-cell leukemia among older populations in Western countries..[Avadhut:2007]{Human}
- B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in Westerners..[Kunihiro:2005]{Human}
- B-cell chronic lymphocytic leukemia (B-CLL), a clonal expansion of B CD5+ cells, is the most frequent type of adult leukemia in western countries..[Monika:2004]{Human}
[chronic lymphocytic leukemia, most]- The most frequent chromosomal aberrations in B-cell chronic lymphocytic leukemia (B-CLL) are deletions on 13q, 11q, and 17p, and trisomy 12, all of which are of prognostic significance..[Urban:2002]{Human}
- Deletions of the long arm of chromosome 11 (11q) are one of the most frequent structural chromosome aberrations in various types of lymphoproliferative disorders. However, in most conventional chromosome banding studies of B-cell chronic lymphocytic leukemia (B-CLL), 11q deletions were not identified as a frequent aberration..[D?hner:1997]{Human}
- B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous malignant disease, both in terms of molecular abnormalities and clinical course. The most frequent chromosomal aberrations in B-CLL are deletions on 13q, 11q, and 17p, and trisomy 12, all of which are of prognostic significance..[Urban:2004]{Human}
[lymphocyte, prognosis]- Spontaneous apoptosis of B-CLL cells in vitro was significantly lower in samples with good prognosis cytogenetics when compared to samples with poor prognosis cytogenetics. In contrast, B-CLL cells from samples with good prognosis cytogenetics exhibited higher basal expression of molecules involved in costimulation, cellular adhesion, and antigen presentation, and induced significantly more T-cell proliferation in mixed lymphocyte cultures..[Jahrsd?rfer:2005]{Human}
[most, prognosis]- On the other hand, most cases without abnormal clones had not received treatment for relatively long periods before and after cytogenetic examination. These findings may indicate that cytogenetic results can be utilized as a parameter for treatment and prognosis in B-CLL..[Sadamori:1984]{Human}
[important, leukemia/leukemias]- In both cases of acute leukemia, the mutation was restricted to one allele and could not be detected in remission samples. Those data suggest that activation of members of the ras oncogene family, typified by K-ras, may be less important in disease pathogenesis in leukemias such as B-CLL that arise from a more committed progenitor..[Browett:1988]{Human}
[most important]- Inactivation of TP53 in 17p13 and deletions in 11q22-q23 have already been shown to be among the most important independent prognostic factors..[Stilgenbauer:1998]{Human}
[leukemia]- Furthermore, we observed a positive correlation between HMTaseI expression levels and stage of leukemia suggesting that changes in the methylation patterns in B-CLL may represent deregulation of the epigenetic repertoire that also include the methylation dependent binding proteins, MBD2 and MeCP2..[Harikrishnan:2005]{Human}
[chronic lymphocytic leukemia/leukemia]- All these abnormalities are characteristic of the B-cell chronic lymphocytic leukemia. In the T-cell leukemia characteristic deletions are 11q22-q23, a.14q23.1, as well as the inversion inv(14)(11q32) and some rarer aberrations..[Karnolsky:2001]{Human}
[chronic lymphocytic leukemia]- Richter syndrome (RS) is well known as a secondary high-grade lymphoma, mostly diffuse large B-cell lymphoma (DLBCL) developed in patients with B-cell chronic lymphocytic leukemia (B-CLL)..[Naoya:2003]{Human}
- This phase II study determined the efficacy and safety of alemtuzumab, a humanized anti-CD52 monoclonal antibody, delivered subcutaneously as first-line therapy, over a prolonged treatment period of 18 weeks in 41 patients with symptomatic B-cell chronic lymphocytic leukemia (B-CLL)..[Jeanette:2002]{Human}
- Allogeneic stem cell transplantation following reduced-intensity conditioning is being evaluated in patients with advanced B-cell chronic lymphocytic leukemia (B-CLL)..[Hoogendoorn:2004]{Human}
- Several authors have studied the T-lymphocyte subpopulations in B-cell chronic lymphocytic leukemia (B-CLL), but previous studies were performed after preceding enrichment procedures, which are known to cause selective losses of certain subpopulations..[Hautekeete:1987]{Human}
- In order to identify regulatory genes involved in the development of an apoptosis-resistant phenotype in patients with chemotherapy refractory B-cell chronic lymphocytic leukemia (B-CLL) expression of apoptosis-regulating genes in B-CLL cells was quantified using cDNA arrays and RT-PCR..[Alejo:2004]{Human}
- We report a case of classical Kaposi's sarcoma (KS) in a patient affected by B-cell chronic lymphocytic leukemia for 2 years and who had not received any antiblastic treatment..[Contu:1986]{Human}
- The true frequency of the CD8-positive B-cell chronic lymphocytic leukemia, any clinical implications, and the possibility of a normal subset of CD5-positive CD8-positive B cells remain to be determined..[Koelliker:1994]{Human}
- The genetic alterations underlying the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) are difficult to assess..[Stilgenbauer:1998]{Human}
- Occurrence of 13q14 deletions between D13S273 and D13S25 in B-cell chronic lymphocytic leukemia (B-CLL) suggests that the region contains a tumor suppressor gene..[van:2003]{Human}
- Results obtained suggest that the relationships between examined soluble form of TNF family proteins may influence the development of B-cell chronic lymphocytic leukemia..[Ewa:2005]{Human}
- In vitro studies were performed in two patients with B-cell chronic lymphocytic leukemia who developed pure red cell aplasia (CLL-PRCA)..[Mangan:1983]{Human}
- In this study we analyse these gene families by quantitative real-time PCR to investigate whether expression levels and the B-cell chronic lymphocytic leukemia (B-CLL) phenotype are associated..[Harikrishnan:2005]{Human}
- We investigated 38 cases of B-cell chronic lymphocytic leukemia (B-CLL) for the presence of non-productive rearrangements in the S(mu) regions and defined for the first time the molecular nature of these rearrangements..[Elena:2002]{Human}
- Our previous studies with B-cell chronic lymphocytic leukemia (B-CLL) have suggested that one of the mechanisms of nitrogen mustard (NM) drug resistance is increased repair of drug-induced damage..[Christodoulopoulos:1999]{Human}
[prognosis]- On analyzing the survival curves of our patients according to different Smlg phenotypes, we found that patients with only mu-type Smlg had a poorer prognosis (P less than .05) than those with mu-type plus delta-type; this difference was even more significant (P less than .01) in patients in stage A, whereas there were no statistical differences in those in stages B and C. Because the appearance of surface heavy chain of delta-type could be an expression of cell maturation, these results suggest that in B-CLL the presence of phenotypically more mature leukemic cells may correlate with better clinical prognosis, particularly in the early phase of the disease..[Baldini:1985]{Human}
- Serum sCD23 is increased in B-CLL patients and can be used in the clinical follow-up of the disease in prediction of the tumor mass and prognosis..[Saka:2006]{Human}
- In conclusion, bright expression of CD20 or sIg light chain is not an unusual feature in B-CLL and may not influence clinical presentation or short-term prognosis..[Tefferi:1996]{Human}
- In conclusion, CGH abnormality was associated with poor prognosis in Japanese B-CLL, and features of Japanese B-CLL, compared to chromosomal abnormalities of Western B-CLL in the literature, include a lower incidence of any abnormality in particular regarding gain of 12q, with the exception of a higher incidence of gains at 3q..[Kunihiro:2005]{Human}
- Moreover no significant correlation between S(mu) deletions and prognosis was observed..[Elena:2002]{Human}
- A probable adverse prognosis is suggested for this group of patients, likely related to clonal evolution..[Christian:2003]{Human}
- Results from patients in stages with equal prognosis (Rai I and II, Rai III and IV) were similar and when these results were grouped the observed differences were highly significant and clearly correlated with all prognostic groups..[Hautekeete:1987]{Human}
[lymphocytes]- The patient presented a complex immunologic deficiency, revealed not only by the monoclonality of the B lymphocytes and their low degree of maturity, but also by the almost total absence of T helper lymphocytes, by the high reduction in NK activity, by the very scarce proliferative response to the polyclonal mitogens PHA, ConA and PWM, and by a complete anergy to the skin test of delayed reactivity..[Contu:1986]{Human}
- This requires more precise research, as new anti-leukemic drugs influence the regulation of apoptosis of neoplastic B lymphocytes..[Monika:2004]{Human}
- Increased numbers of T lymphocytes were present in marrow aspirates of these patients..[Mangan:1983]{Human}
- Surprisingly, we did not observe significant changes in DNMT1 expression in B-CLL cases when compared to normal lymphocytes, regardless of whether we normalise against GAPDH or PCNA as reference standards..[Harikrishnan:2005]{Human}
[class]- In contrast to primary B-CLL cells as stimulator cells, these malignant APCs were capable of inducing the generation of B-CLL-reactive CD8(+) CTL lines and clones from HLA class I-matched donors..[Hoogendoorn:2004]{Human}
- By applying different algorithms, the data enabled an efficient class discrimination of the V(H)3-21+ subset based on 27 or 57 genes..[Susann:2005]{Human}
[chronic]- All patients experienced acute and chronic graft-versus-host disease and responded clinically to SCT..[Mattsson:2000]{Human}
[inferior]- The B-CLL subgroups with chromosome 11q23 deletion have been associated with aggressive disease course involving ATM deletion, extensive bulky lymphadenopathy (BLA), and inferior clinical outcome..[Avadhut:2007]{Human}
- We conclude that deletions in 6q21 occur in 7% of B-CLL and identify a subgroup of patients characterized by a larger tumor mass but no inferior outcome..[Stilgenbauer:1999]{Human}
[important]- Prolonged treatment is important for maximal bone marrow response..[Jeanette:2002]{Human}
- It is important that these changes are seen not only with CpG ODN but with ODN that lack the classical CpG motif..[Bernd:2005]{Human}
- The elucidation of these abnormalities in the circulating non-malignant immune cells of B-CLL patients has generated important insights into the biology of the disease..[Bartik:1998]{Human}
- We stress that immunosuppression may play an important role in the pathogenesis of both diseases and the possibility of their being conditioned by common genetic HLA-associated factors of predisposition..[Contu:1986]{Human}
- Several candidates, such as mutation of p53 gene and abnormalities of cyclin dependent kinase inhibitor, have been proposed to play an important role in the transformation of a part of B-CLL..[Naoya:2003]{Human}
- A durable anti-leukemic effect was probably important in these patients..[Mattsson:2000]{Human}
- Addition of CD38 to the flow cytometry antibody panel for B-CLL analysis is a relatively easy way to obtain important prognostic information..[Boonstra:2005]{Human}
- Deoxynucleoside kinases are key enzymes in deoxyribonucleoside salvage, activating several clinically important chemotherapeutic drugs..[Eriksson:1994]{Human}
- We conclude that bfl-1 may be an important regulator of B-CLL apoptosis, which could contribute to disease progression and resistance to chemotherapy, and as such represent a future potential therapeutic target..[Alejo:2004]{Human}
- Tumor necrosis factor (TNF) superfamily, involving membrane receptors and ligands are important for the growth and survival of leukemic B cells..[Ewa:2005]{Human}
[lymphocyte]- Two of the four previously untreated patients responded with transient (90%) decreases in absolute lymphocyte counts lasting for 2 and 7 months..[Schulof:1985]{Human}
- Seventy-eight percent of the B-CLL patients with lymphocyte doubling time (LDT) <12 months and 24% of patients with LDT >12 months had high sCD23 levels (P = 0.008)..[Saka:2006]{Human}
[classification]- Serum levels of IgG, IgA and IgM were assayed simultaneously and findings were correlated with clinical stage (Rai classification)..[Hautekeete:1987]{Human}
[classified]- CD20 intensity was classified as weak in 62% of patients, moderate in 12%, and strong in 26%..[Tefferi:1996]{Human}
[most]- The most frequent abnormality was 13q14.3 deletion, which was detected in 26 (32.9%) patients..[Beyhan:2008]{Human}
- As detected by the interphase cytogenetic FISH approach, the most common chromosome abnormalities of B-CLL are deletions in band 13q14, followed by deletions in 11q22-q23, trisomy 12, deletions in 17p13, and deletions in 6q21..[Stilgenbauer:1998]{Human}
- Deletions affecting the long arm of chromosome 6 (6q) are among the most commonly observed chromosomal aberrations in lymphoid malignancies and have been identified as adverse prognostic factor in subsets of tumors..[Stilgenbauer:1999]{Human}
- They have become the most commonly used markers to trace loss of heterozygosity in tumors..[Urban:2004]{Human}
- Short telomere length and high telomerase activity were significantly associated with a shorter median survival (P=0.02 and P <0.001), and telomerase activity was the most significant prognostic factor for overall survival in B-CLL (P <0.001)..[Bechter:1998]{Human}
- The most frequent changes observed were gains of chromosomes 3q in five cases (19%) and 17q in three cases (12%)..[Kunihiro:2005]{Human}
- By FISH, the most common chromosome abnormalities are deletions of 13q followed by deletions of 11q, trisomy 12, and deletions of 17p..[D?hner:1997]{Human}
- We conclude that IS ODN including CpG ODN can induce apoptosis of most B-CLL samples..[Bernd:2005]{Human}
- Forty-three of the 214 (20%) tumors exhibited 11q deletions; 11q deletions were the second most frequent chromosome aberration following 13q14 (RB1 and/or D13S25) deletions (45%); they were more frequent than trisomy 12 (15%) or deletion of 17p (TP53 gene) (10%)..[D?hner:1997]{Human}
- At the HLA typing, the patient was DR5, as are most classical KS and/or B-CLL patients..[Contu:1986]{Human}
- Long-distance PCRs localized the S(mu) deletions in the V(H)DJ(H) rearranged allele in most cases..[Elena:2002]{Human}
- Abnormalities of chromosomes 11 and 14 were most frequently involved in RS, but non-specific..[Naoya:2003]{Human}
- We examined the most optimal method to transform B-CLL cells into efficient antigen-presenting cells (APC) using activating cytokines, by triggering toll-like receptors (TLRs) using microbial pathogens and by CD40 stimulation with CD40L-transfected fibroblasts..[Hoogendoorn:2004]{Human}
- By performing a supervised clustering of genes that most strongly discriminated between rB-CLL vs. sB-CLL a small group of genes was identified, where bfl-1 was the strongest discriminating gene (p < 0.05), with higher expression in rB-CLL..[Alejo:2004]{Human}
- Whereas IgVH mutational status is a time consuming and demanding technique, only available in a limited number of centres, CD38 expression by flow cytometry is relatively simple and rapidly obtained in most diagnostic laboratories..[Tryfonia:2004]{Human}
- Recent publications have focused on two of the genes that most likely do not have a tumor suppressor role..[van:2003]{Human}
- We conclude that RFP2, c13ORF1, and a chromosome 13-specific ST13-like gene, FAM10A4, are the most likely candidates for such a type of B-CLL TSG..[van:2003]{Human}
- High levels of tumor necrosis factor-alpha (TNF-alpha) and soluble interleukin-2 receptor (sIL-2R) indicated advanced disease, and patients with increased levels pre- and post-SCT were also those with the most long-lasting PCR-detectable MRD post-SCT..[Mattsson:2000]{Human}
- One of the most perplexing questions regarding epigenetic modifications and leukemogenesis is the relationship with DNA methyltransferases (DNMT's)..[Harikrishnan:2005]{Human}
- Allelic loss of 13q14 was observed in 63.2% patients, most of them showing D13S319 and D13S25 deletion; 11% of patients showed TP53 monosomy..[Christian:2003]{Human}
|
| - We determined the expression levels of the mdr1 and mdr3 multidrug-resistance genes (also known as PGY1 and PGY3, respectively) in peripheral blood cells from 69 adult patients with acute and chronic leukemias, using an RNase protection assay. Expression of mdr1 was found in samples from patients with acute nonlymphocytic leukemia (13 of 17), chronic myelocytic leukemia (CML, chronic phase, 10 of 10; blast crisis, three of four), acute lymphocytic leukemia (ALL, eight of 11), B-cell chronic lymphocytic leukemia (B-CLL, 17 of 17), hairy cell leukemia (HCL, one of two), and T-cell prolymphocytic leukemia (one of one), but not in B-cell prolymphocytic leukemia (B-PLL, 0 of seven). Expression of mdr3 was only detected in samples from B-cell lymphocytic leukemias: CML, lymphoid blast crisis (one of one), B-cell ALL (two of two), B-CLL (17 of 17), B-PLL (seven of seven), and HCL (two of two). In vitro drug uptake studies by on-line flow cytometry showed that in leukemia cells expressing either mdr1 or mdr3, the steady-state accumulation of daunorubicin could be significantly increased by addition of cyclosporine and, to a lesser extent, by verapamil. Because cyclosporine and verapamil are known as inhibitors of the mdr1-encoded P-glycoprotein drug-efflux pump, and because the mdr1 and mdr3 genes are highly homologous, our data suggest that the mdr3 gene encodes a functional drug pump in B-cell lymphocytic leukemias. The results of this study may have implications for clinical therapy for acute or chronic leukemias expressing the mdr1 or mdr3 gene, in particular, treatment with combinations of cytotoxic drugs plus agents that reverse multidrug resistance. Since mdr1 and mdr3 are frequently expressed in untreated as well as treated leukemia, such combination therapy should be considered for untreated patients as well as treated patients..[Herweijer:1990]{Human}
- To define further the role of marrow T suppressor lymphocytes in the pathogenesis of the hypoproliferative anemia in all Rai clinical stages of B cell chronic lymphocytic leukemia ( CLL), marrow erythroid progenitor cell (CFU-E and BFU-E) frequency, marrow T gamma lymphocyte frequency per 1,000 nucleated marrow cells, and T cell-erythroid progenitor cell interactions were examined in 30 CLL patients and normal control subjects..[Mangan:1985]{Human}
- Recent reports of successfully completed cytogenetic studies using polyclonal B-cell activators demonstrate that trisomy-12 and 14 q+ are the most frequently observed chromosomal abnormalities in B-cell chronic lymphocytic leukemia ( CLL). It appears that when trisomy-12 is accompanied by yet another abnormality, the prognosis of patients is uniformly poor. Patients in early stages of CLL retain delayed hypersensitivity reactivity, while those in advanced stages are usually anergic. The lymphocytes from venous blood of patients with CLL appear to retain at least some ability to respond to stimulation with mitogens in early stages, whereas in advanced stages they show no response to mitogens. Serum immunoglobulin levels are normal in the early (0 and I) stages, are markedly decreased in the advanced (III and IV) stages, and are somewhat between these extremes in the intermediate (II) stage of CLL. Prolymphocytic leukemia and prolymphocytoid transformation of CLL are indicators of poor prognosis, while a morphological variant characterized by large granular lymphocyte is associated with good prognosis. At this time it is not possible to ascribe strong prognostic significance to phenotypic features of lymphocytes in B-CLL; however, studies currently in progress may soon provide important insights on this subject..[Rai:1987]{Human}
- We investigated the effects of stromal cells, obtained from lymph nodes with various lymphoid disorders and characterized immunocytochemically as fibroblasts, on the maturation of a cell line "HN" established from an atypical PLL (prolymphocytic leukemia) having phenotypic characteristics of both CLL ( chronic lymphocytic leukemia) and HCL (hairy cell leukemia). Coculture with stromal cells, irrespective of the kind of lymphoid disease affecting the lymph node, induced a plasmacytoid cytology in HN cells, an increase of cIg gamma, and decreases of sIg gamma, CD5, CD21, HC2, and B-ly7..[Takeuchi:1995]{Human}
- The most common human leukemia is B cell chronic lymphocytic leukemia ( CLL), a malignancy of mature B cells with a characteristic clinical presentation but a variable clinical course. The rearranged immunoglobulin (Ig) genes of CLL cells may be either germ-line in sequence or somatically mutated. Lack of Ig mutations defined a distinctly worse prognostic group of CLL patients raising the possibility that CLL comprises two distinct diseases. Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression "signature," irrespective of Ig mutational status, suggesting that CLL cases share a common mechanism of transformation and/or cell of origin..[Rosenwald:2001]{Human}
- Deletions or translocations of 13q, most commonly involving band 13q14, belong to the most frequent structural chromosome abnormalities in B-cell chronic lymphocytic leukemia (B-CLL). In a combined metaphase and interphase cytogenetic study using conventional G-banding analysis and fluorescence in situ hybridization (ISH) we previously analysed the retinoblastoma susceptibility gene (RB-1) and its chromosomal locus 13q14 in 35 patients with chronic B-cell leukemias. We report here on the interphase cytogenetic analysis of 109 cases with chronic B-cell leukemias [B-CLL = 90; B-prolymphocytic leukemia (B-PLL) = 6, hairy cell leukemia (HCL) = 13]; a subset of 49 patients (B-CLL = 45; B-PLL = 4) was studied by conventional G-banding analysis..[D?hner:1995]{Human}
- The expression of a series of adhesion receptors: L-selectins (CD62L): Leu-8, several integrins (LFA-1: CD11a/CD18, VLA-4: CD49d/CD29 and VLA-5: CD49e/CD29), ICAM-1(CD54) and the 'homing receptor' (CD44) were investigated by a dual color flow cytometry in 56 cases of B cell disorders namely, 39 chronic lymphocytic leukemias ( CLL), four hairy cell leukemia (HCL), seven splenic lymphoma with villous lymphocytes (SLVL) and six other non-Hodgkin's lymphoma (NHL)..[Csanaky:1997]{Human}
- B-cell chronic lymphocytic leukemia ( CLL) is a highly common form of leukemia characterized by the accumulation of long-lived, functionally inactive, mature appearing neoplastic B lymphocytes. In addition, immune disturbances such as hypogammaglobulinemia and autoimmune phenomena (particularly, autoimmune hemolytic anemia) are frequently found in CLL patients [1-2]. The etiology of CLL is unknown. In contrast with other leukemias, there is no relationship between CLL and exposure to radiation or other cytotoxic agents. A genetic basis is highly likely since there are differences in the incidence of CLL in different countries (e.g., CLL accounts for 30%-40% of all the leukemias in Western countries as compared to 5%-10% in Asian countries) and the risk of contracting CLL is higher among persons with first-degree relatives with the disease [3]. Because the incidence of CLL increases with age and the longer life expectancy of the general population, the age of patients at diagnosis is increasing..[Montserrat:1997]{Human}
- B-cell chronic lymphocytic leukemia (B-CLL) is characterized by highly variable distribution of tumor mass between peripheral blood, bone marrow and lymphoid organs which is important for staging, classification and prognosis. These clinical findings with novel data about importance of B-cell receptor and its stimulation with the support of microenvironment indicate important role of tissues (lymphoid organs and bone marrow) in the pathogenesis of B-CLL. Here is presented the novel approach of simultaneous characterization of B-CLL cells form peripheral blood, bone marrow and lymph nodes by flow cytometry and immunocytochemistry, defining inter- and intraclonal diversity with respect to various molecules..[Ozren:2010]{Human}
- B-cell chronic lymphocytic leukemia ( CLL) is the most common human leukemia. Deregulation of the T-cell leukemia/lymphoma 1 oncogene (TCL1) in mouse B cells causes a CD5(+) leukemia similar to aggressive human CLL..[Alexey:2012]
- The classification of CD5-negative/CD10-negative chronic B-cell leukemias (CD5-/CD10- CBL) can be problematic. Most of these cases may represent leukemic non-Hodgkin's lymphoma (NHL) other than B-cell chronic lymphocytic leukemia (BCLL); nonetheless, some investigators still advocate the term "CD5-negative BCLL." Because adhesion molecule (AdMol) expression patterns reflect the biology of lymphoid neoplasms, we studied a series of 106 B-cell lymphoproliferative disorders, including CD5+ BCLL (n = 56), NHL other than BCLL (n = 35), and CD5-/CD10- CBL (excluding hairy cell leukemia and prolymphocytic leukemia) with no prior history of NHL (n = 15) for expression of components of the very late antigen-4 complex (alpha4/beta1 integrin (CD49d/CD29)), components of the mucosal addressin-cell adhesion molecule receptor (alpha4(CD49d)/beta7 integrin), and L-selectin (CD62L)..[Finn:2001]{Human}
- Therapeutic options are limited and the prognosis is poor for patients with fludarabine-refractory B-cell chronic lymphocytic leukemia ( CLL). Bortezomib induces apoptosis in vitro in CLL cells, both alone and in combination, including in cells resistant to fludarabine or other agents. The aim of the current randomized, open-label, Phase II study was to investigate the clinical activity of bortezomib in patients with fludarabine-refractory B-cell CLL..[Stefan:2006]{Human}
- This well-documented acquired anomaly is one of the most specific numerical chromosome alterations to occur in human hematological malignancies. We have cytogenetically characterized bone marrow and peripheral blood cells from a patient with B-cell chronic lymphocytic leukemia ( CLL) having a unique acquired translocation involving chromosomes 6 and 12, t(6;12) (p21.3;q13), which implicates band 12q13 as the site of the gene(s) important in this lymphoproliferative B-cell disorder. Aneuploidy, in the form of trisomy of chromosome 12, is not a requirement for neoplastic transformation in B-cell CLL, but gene rearrangement (present case) or nondisjunctional acquisition of additional copies of defective genes on chromosome 12 at band q13 may be involved in the genesis or progression of this disorder..[Stock:1999]{Human}
- B-cell chronic lymphocytic leukemia (B-CLL) is the most common B-cell leukemia among older populations in Western countries..[Avadhut:2007]{Human}
- Soluble CD23 (sCD23) and beta-2 microglobulin (beta2-m) are reliable prognostic parameters in B-cell chronic lymphocytic leukemia ( CLL); however, their merit over well-established clinical variables such as clinical stages, bone marrow (BM) histology and lymphocyte doubling time (LDT) remains to be defined..[Molica:1999]{Human}
- Peripheral blood lymphocyte morphology and karyotype were correlated across the spectrum of cytogenetic abnormalities in 78 previously karyotyped cases of B-cell chronic lymphocytic leukemia ( CLL). Cases were classified according to French-American-British morphologic criteria as typical CLL or CLL, mixed-cell type; the latter category was divided into CLL with a mixture of small and large cells and CLL with increased prolymphocytes ( CLL/PL)..[Kroft:1997]{Human}
- It has been reported that telomeres are shortened in acute leukemias where the cell turnover is high. B-cell chronic lymphocytic leukemia ( CLL) is a particularly interesting haematological malignancy in regard to telomere dynamics because most of the malignant cells in CLL are mitotically inactive. In this study, we analysed the telomere length in patients with B-cell CLL in a comparison with the control group by using ddPRINS technique..[Sukru:2006]{Human}
- B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in Western countries and results from the accumulation of B-lymphocytes which are functionally abnormal and predominantly non-cycling in vivo. Consequently, it is important to understand why B-CLL cells accumulate in GO phase. Since TGF-beta is an important negative regulator of the immune system, a loss of responsiveness to this factor might provide a selective advantage to B-CLL cells..[Lagneaux:1998]{Human}
- We propose that lymph node stromal cells play an important role in the differentiation of B cells through direct contact and that HN cells will be useful for investigating the differentiation pathway of chronic B cell leukemia cells..[Takeuchi:1995]{Human}
- Strong evidence exists for an association between high vascular endothelial growth factor (VEGF) levels and poor prognoses in patients with solid tumors and acute leukemia. Using Western blot analysis and solid-phase radioimmunoassay, we measured cellular VEGF levels in B-cell chronic lymphocytic leukemia ( CLL) samples from 225 patients and correlated these levels with disease characteristics and prognoses. The median VEGF level in CLL samples was 7.26 times the median level detected in normal peripheral blood mononuclear cells..[Aguayo:2000]{Human}
- B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in Westerners..[Kunihiro:2005]{Human}
- Granulomatous cutaneous reactions are well described in association with T-cell non-Hodgkin lymphoma and Hodgkin lymphoma, but are rarely seen in association with B-cell non-Hodgkin lymphoma or leukemia. We report a case of a 65-year-old woman with B-cell chronic lymphocytic leukemia ( CLL)/small lymphocytic lymphoma (SLL) who presented with multiple, tender, firm pink papules on the face, upper trunk and upper extremities 6 years after diagnosis of CLL. Biopsy revealed both palisading granulomatous dermatitis consistent with actinic granuloma and a dense perivascular lymphocytic infiltrate consistent with the patient's known history of leukemia. This is an unusual manifestation of cutaneous B-cell CLL that is rarely seen..[Julia:2012]
- B-cell chronic lymphocytic leukemia (B-CLL), a clonal expansion of B CD5+ cells, is the most frequent type of adult leukemia in western countries..[Monika:2004]{Human}
- B-cell chronic lymphocytic leukemia ( CLL) is a clinically heterogeneous disease with many patients surviving for decades with minimal or no treatment, whereas others succumb rapidly to their disease despite therapy. In recent years, new molecular prognostic factors have emerged in CLL that have significantly improved the subgrouping of the disease. One of the most important molecular predictors, the immunoglobulin V(H) gene mutation status, divides CLL into two prognostic groups, depending on the presence or absence of somatic hypermutation, where unmutated V(H) genes are associated with considerably worse prognosis than mutated V(H) genes. An exception to this appears to be CLL patients utilizing the V(H)3-21 gene as they have poor outcome irrespective of mutation status..[Gerard:2005]{Human}
- The original observation that sera from patients with chronic B-cell lymphocytic leukemia (B-CLL) contain high amounts of soluble CD23 (sCD23), which reflect disease activity and tumor load has been confirmed by numerous reports and serial determinations of sCD23 are now recognized as important indicators of disease progression..[Schwarzmeier:2004]{Human}
- B-cell chronic lymphocytic leukemia ( CLL) can be classified as typical or atypical based on morphologic and immunophenotypic features..[O'Connor:2000]{Human}
- The most frequent chromosome aberrations in B cell chronic lymphocytic leukemia (B-CLL) detected by conventional chromosome banding analysis are trisomy 12 followed by structural abnormalities of the long arms of chromosomes 13, 14, and 11. Complex karyotypes, trisomy 12, and a '14q+' abnormality have been associated with inferior prognosis, whereas aberrations of 13q have been found in patients with a favorable outcome..[D?hner:1997]{Human}
- One of the main reasons for interest in these molecules is that they may play a determining role in neoplastic transformation and diffusion; in particular, in lymphoproliferative syndromes, a lack of cell adhesiveness or an abnormal adhesion pattern in neoplastic lymphocytes may free these cells from regulation, thus contributing towards the development of leukemia and/or lymphoma. Studies of VLA expression in B-cell leukemia/lymphomas show a modulation of VLA3 and VLA4 reactivity. The most interesting element is the identification of a VLA3/VLA4 pattern associated with B-cell chronic lymphocytic leukemia (B-CLL) characterised by a reduced expression of VLA4 and the constant expression of VLA3..[Baldini:1994]{Human}
- Leukemia cell survival also could be enhanced by exogenous IFN-gamma or anti-CD40 presented on Fc gamma RII (CDw32)-expressing L cells, but not by exogenous IL-4, IL-6, or monomeric human IgG. We find that Ag acts directly on the leukemia B cells to inhibit apoptosis. This effect could be mimicked by cross-linking the leukemia cells' surface IgM receptors with immobilized murine mAb specific for human Ig mu-chains, but not by immobilized mAb of irrelevant specificity. In contrast to most follicular NHL, this leukemia B cell population does not have evidence of bcl-2 gene rearrangement. Also, in contrast to non-Hodgkin's lymphomas and most B cell CLL, these cells do not express detectable amounts of bcl-2. Finally, although capable of inhibiting apoptosis, surface Ig receptor cross-linking does not induce expression of bcl-2 in these variant leukemia cells. We hypothesize that the lack of bcl-2 expression may render these leukemia cells particularly dependent upon the survival signal(s) derived from surface Ig receptor cross-linking. This state may represent an early stage in leukemia/lymphomagenesis, possibly accounting for the intraclonal diversity observed in the Ig V genes expressed by certain CD5- B cell leukemias and lymphomas..[Kobayashi:1994]{Human}
- A role for ATM in the development of sporadic T-cell chronic leukemias is supported by the finding of loss of heterozygosity at 11q22-23 and ATM mutations in leukemias carrying TCL-1 rearrangements. Approximately 14% of B-cell chronic lymphocytic leukemia (B-CLL), the most common adult leukemia, carry deletions of the long arm of chromosome 11 at 11q22-23. Loss of heterozygosity at 11q22-23 and, more recently, absence of ATM protein, have been associated with poor prognosis in B-CLL..[Bullrich:1999]{Human}
- Most B-cell chronic lymphocytic leukemias and a small normal subset of B lymphocytes express the T-cell-associated CD5 antigen; expression of other T-cell antigens has been reported only rarely. The authors report two cases of typical B-cell chronic lymphocytic leukemia, seen during 1 year, in which two-color flow cytometric analysis documented expression of the T-cell-associated CD8 antigen by the monoclonal B cells..[Koelliker:1994]{Human}
- We studied a variant CD5- B cell chronic lymphocytic leukemia ( CLL) cell population that produces pathologic IgM kappa rheumatoid factor autoantibodies. In contrast to common CD5+ B cell CLL, this variant leukemia cell population displays intraclonal diversity in its expressed Ig V genes, similar to that noted for follicular B cell non-Hodgkin's lymphomas. Also, in contrast to common B cell CLL, these leukemia cells rapidly undergo cell death hours after being placed in tissue culture..[Kobayashi:1994]{Human}
- Most of these genes code either for cell adhesion molecules (L-selectin, integrin-beta2) or for factors inducing cell adhesion molecules (IL-1beta, IL-8, EGR1), suggesting that prognosis of this disease may be related to a defect in lymphocyte trafficking..[Stratowa:2001]{Human}
- Fifty-three patients affected with B-cell chronic lymphocytic leukemia ( CLL) younger than 50 years and observed in two hematological institutions have been retrospectively evaluated in order to verify whether this disease has different clinico-hematological features at presentation and different prognosis as compared to older cases. In our experience young cases with B-CLL diagnosis, confirmed by immunophenotype in 90.5% of patients, accounted for 7.1% of the whole CLL population..[Molica:1994]{Human}
- One leiomyosarcoma and one extra-skeletal osteosarcoma showed a dCK levels comparable to those found in normal lymphocytes (84 +/- 6 and 109 +/- 4 ng/mg), while other sarcoma samples contained levels comparable to the gastrointestinal adenocarcinomas (20 +/- 7 ng/mg, n = 12). We confirm that dCK is expressed constitutively and predominantly in lymphoid cells, but conclude that a significant expression may be found in non-lymphoid tissues as well, with increased levels in the corresponding tumor tissue. 2-Chlorodeoxyadenosine (CdA), an antileukemic agent used in treatment of hairy cell leukemia and chronic lymphocytic leukemias (B-CLL), is phosphorylated by dCK which was used as the selective substrate for this enzyme..[Eriksson:1994]{Human}
- The coexistence of acute myeloid leukemia and chronic lymphocytic leukemia in the same patient is rare. The majority of the cases correspond to patients that developed acute leukemia during the evolutionary course of a chronic lymphatic leukemia following treatment with chemotherapy drugs. We report a case of acute myelomonocytic leukemia concurrent with untreated B-cell chronic lymphocytic leukemia in which the use of flow cytometry analysis with a large panel of monoclonal antibodies, allowed the demonstration of different pathological populations and determine immunophenotyping patterns. Published cases of simultaneous chronic lymphocytic leukemia and acute leukemia are reviewed..[Viviana:2010]{Human}
- B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma ( CLL/SLL) may involve the bone marrow in nodular, interstitial, diffuse, or mixed patterns. However, B-cell CLL/SLL associated with large reactive germinal centers (the so-called interfollicular pattern) involving the bone marrow is not reported. We describe 2 examples of B-cell CLL/SLL that subtotally replaced the bone marrow with an interfollicular pattern..[Kim:2000]{Human}
- Trisomy of chromosome 12 is one of the commonest cytogenetic abnormalities in the karyotype in chronic lymphocytic leukemia ( CLL). It is associated with atypical morphology of lymphocytes, progressing disease and poor survival. A high incidence abnormality in the B-cell CLL is deletion of chromosome 13 (13q14) detected by using modern diagnostic methods such as southern blot hybridization and fluorescence in situ hybridization. It occurs in 51% of the CLL patients and in as much as 70% in mantle-cell lymphoma..[Karnolsky:2001]{Human}
- B cell chronic lymphocytic leukemia ( CLL) is a disease of expanding monoclonal B cells whose B cell receptor (BCR) mutational status defines 2 subgroups; patients with mutated BCRs have a more favorable prognosis than those with unmutated BCRs. CLL B cells express a restricted BCR repertoire including antibodies with quasi-identical complementarity-determining region 3 (CDR3), which suggests specific antigen recognition. The antigens recognized by CLL antibodies may include autoantigens since about half of CLL B cells produce autoreactive antibodies. However, the distribution of autoreactive antibodies between Ig heavy-chain variable-unmutated (IgV-unmutated) CLL (UM-CLL) and IgV-mutated CLL (M-CLL) is unknown. To determine the role of antibody reactivity and the impact of somatic hypermutation (SHM) on CLL antibody specificity, we cloned and expressed in vitro recombinant antibodies from M- and UM-CLL B cells and tested their reactivity by ELISA. We found that UM-CLL B cells expressed highly polyreactive antibodies whereas most M-CLL B cells did not. When mutated nonautoreactive CLL antibody sequences were reverted in vitro to their germline counterparts, they encoded polyreactive and autoreactive antibodies. We concluded that both UM-CLLs and M-CLLs originate from self-reactive B cell precursors and that SHM plays an important role in the development of the disease by altering original BCR autoreactivity..[Maxime:2005]{Human}
- The most frequent chromosomal aberrations in B-cell chronic lymphocytic leukemia (B-CLL) are deletions on 13q, 11q, and 17p, and trisomy 12, all of which are of prognostic significance..[Urban:2002]{Human}
- The goal of this study was to evaluate the relation of chromosomal abnormalities detected by fluorescence in situ hybridization (FISH) in the prognosis of B-cell chronic lymphocytic leukemia (B-CLL) patients..[Beyhan:2008]{Human}
- The usage of the immunoglobulin (Ig) V(H)3-21 gene is associated with poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) despite V(H) gene mutation status..[Susann:2005]{Human}
- To establish xenograft models of human B-cell chronic lymphocytic leukemia ( CLL), we inoculated 5 x 10(6) D10-1 cells, a subline of Epstein-Barr virus (EBV)-transformed human B-cell CLL with a marker chromosomal anomaly, into SCID or irradiated nude mice by the intravenous (i.v.) or intraperitoneal (i.p.) route..[Zhu:1994]{Human}
- Soluble CD23 (sCD23) was proposed as a marker of disease activity and as an important prognostic parameter in B-cell chronic lymphocytic leukemia (B-CLL)..[Saka:2006]{Human}
- The chromosome constitutions of stimulated lymphocytes in 21 untreated cases with B-cell chronic lymphocytic leukemia (B-CLL) were examined..[Sadamori:1984]{Human}
- Mutations of exons 5 to 8 of the p53 gene were looked for in 39 cases of B-cell chronic lymphocytic leukemia ( CLL) using polymerase chain reaction single-strand conformation polymorphism analysis and DNA sequencing..[Fenaux:1992]{Human}
- In order to obtain more information on the pattern of CD11c-positivity in otherwise typical B-cell chronic lymphocytic leukemia ( CLL), we analyzed immunological and clinico-pathological features of 99 such patients studied with two different monoclonal antibodies (MoAbs)..[Molica:1995]{Human}
- Deletions of the long arm of chromosome 11 (11q) are one of the most frequent structural chromosome aberrations in various types of lymphoproliferative disorders. However, in most conventional chromosome banding studies of B-cell chronic lymphocytic leukemia (B-CLL), 11q deletions were not identified as a frequent aberration..[D?hner:1997]{Human}
- These genes may be important in the development of nitrogen mustard (NM) drug resistance in B-cell chronic lymphocytic leukemia (B-CLL). Using Western blot analysis, we examined the levels of Bcl-2, Bax, Bcl-X and p53 protein expression and determined whether the levels of these proteins correlated with in vitro drug resistance in CLL patients' lymphocyte samples. Our investigations suggest that in CLL, NM drug resistance develops without any detectable alteration of Bcl-2, Bax or Bcl-X..[Christodoulopoulos:1998]{Human}
- Following allogeneic stem cell transplantation (SCT), we studied the presence of donor and recipient derived cells within the CD19+ B cell fraction, in patients with B cell chronic lymphocytic leukemia ( CLL)..[Mattsson:2000]{Human}
- The surface phenotype of these cells was identical to that of circulating lymphocytes, indicating meningeal involvement of leukemia, a rare complication in B-CLL. At the time of this WBC elevation, 24% of circulating lymphocytes had prominent nucleoli, indicating progression of the disease to CLL/prolymphocytic leukemia..[Naoko:2005]{Human}
- The genetic features of B-cell chronic lymphocytic leukemia ( CLL) are currently being reassessed by molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH). Conventional cytogenetic studies by chromosome banding are difficult in CLL mainly because of the low in vitro mitotic activity of the tumor cells, which leads to poor quantity and quality of metaphase spreads. Molecular genetic analyses are limited because candidate genes are known for only a few chromosomal aberrations that are observed in CLL. FISH was found to be a powerful tool for the genetic analysis of CLL as it overcomes both the low mitotic activity of the CLL cells and the lack of suitable candidate genes for analysis..[Stilgenbauer:2001]{Human}
- CD5+, CD23+) B-cell chronic lymphocytic leukemia ( CLL). Although changes of CD20 antigen density did not correlate with clinical parameters representative of either tumor mass (i.e. clinical stage, histological pattern of bone marrow involvement, absolute peripheral blood lymphocytosis) or disease progression (i.e. lymphocyte doubling time), a trend toward a better life-expectancy was observed in the low CD20 expression group compared with the high CD20 expression group (p = 0.05; relative risk of death, 0.51, 95% confidence interval, 0.24-1.04)..[Molica:1998]{Human}
- However, a recent report indicated that VH251, one of three VH genes belonging to the VH5 subgroup (e.g., VH251, VH32, and VH15), not only is frequently rearranged in this disease, but also has extensive and selective mutations when expressed by CLL B cells. The extent and nature of these mutations contrasts markedly from the low level of mutations noted in VH5 genes used by normal B cells or other Ig V genes found expressed in CLL. To determine whether this difference reflects a unique property of VH251 or a previously unrecognized subgroup of CLL, we examined for VH5 Ig gene rearrangements in leukemia cells from 68 patients that satisfied clinical and diagnostic criteria for CD5+ B cell CLL. Southern blot hybridization studies with probes for VH251 and the JH locus revealed that only 7 (10%) of the 68 monoclonal CLL cell populations had undergone Ig gene rearrangement involving VH5 genes. Two (3%) were found to have functionally rearranged VH5 genes that shared > or = 98% sequence homology with 5-2R1, a VH251 gene isolated from a pre-B cell acute lymphocytic leukemia. The other five CLL (7%) had functionally rearranged VH5 genes that each shared > or = 99% nucleic acid sequence homology with a germline VH32 isolated from human sperm DNA..[Rassenti:1993]{Human}
- We performed a feasibility study systematically comparing large-scale gene expression profiles with clinical features in human B-cell chronic lymphocytic leukemia (B-CLL). cDNA microarrays were employed to determine the expression levels of 1,024 selected genes in 54 peripheral blood lymphocyte samples obtained from patients with B-CLL..[Stratowa:2001]{Human}
- High levels of dCK were found in normal mononuclear leukocytes (91-145 ng dCK/mg protein) and in B-cell chronic lymphocytic leukemia (80 +/- 30 ng/mg, n = 23). Hairy cell leukemia contained lower levels (28 +/- 23 ng/mg, n = 7), as did unexpectedly three samples of T-cell chronic lymphocytic leukemia (18 +/- 14 ng/mg). Phytohemaglutinine stimulation of normal lymphocytes did not lead to any substantial increase in either dCK activity or expression (less than 2.5-fold)..[Eriksson:1994]{Human}
- T-lymphocyte colony formation in agar culture was investigated in 20 untreated B-cell Chronic Lymphocytic Leukemia ( CLL) patients in stage O. As compared to the controls, colony growth was very poor when unseparated peripheral-blood lymphocytes from CLL-patients were seeded. The number of colonies was greatly higher when T-cell enriched fractions from CLL were plated; however, they failed to reach the normal range even in this experimental condition..[Neri:1982]{Human}
- In this report, we have examined the expression and distribution of HsRad51 protein in lymphocytes from patients with B-CLL to see whether the expression of HsRad51 is associated with NM damage to the malignant B lymphocytes, specifically chlorambucil (CLB), which is the standard alkylating agent used to treat patients with B-CLL. We have analyzed the intracellular distribution of HsRad51 protein in these lymphocytes before and after treatment with CLB by immunofluorescence. In vitro CLB treatment induces Rad51 expression, as measured by increased immunopositive staining in all CLL samples. In the CLB-resistant CLL lymphocytes, there was a linear correlation between induction of Rad51 protein at 5.4 microM CLB and the in vitro LD50 dose of CLB. Surprisingly, although it has been reported that Rad51 is induced in S phase and only 10% of cells from cell lines expressed positive immunostaining for Rad51, our CLL lymphocytes, which were not subjected to in vitro drug exposure, were 90% positive for Rad51, despite their nonproliferative state, which suggests that there is chronic activation of the protein. Our results suggest that CLB activates HsRad51-directed recombination repair and that this process may be important in NM drug-induced cytotoxicity..[Christodoulopoulos:1999]{Human}
- In B-cell chronic lymphocytic leukemia (B-CLL) the Rai and Binet staging criteria are not always able to accurately predict the prognosis of each patient..[Boonstra:2005]{Human}
- In a prospective study, peripheral lymphocytes of 93 previously untreated patients with B-cell chronic lymphocytic leukemia (B-CLL) were evaluated with flow cytometry for the intensity of CD20 and surface immunoglobulin (sIg) light-chain (LC) expression..[Tefferi:1996]{Human}
- We previously demonstrated that treatment of B cell chronic lymphocytic leukemia (B-CLL) cells with one class of IS ODN, CpG ODN, alters their phenotype and increases their immunogenicity..[Bernd:2005]{Human}
- All the tumor-inoculated mice had histologically confirmed metastases in lymph nodes, and most of them also had metastases in one or more internal organs..[Zhu:1994]{Human}
- Chromosomal abnormalities in B-cell chronic lymphocytic leukemia (B-CLL) have been shown to correlate with prognosis..[Jahrsd?rfer:2005]{Human}
- B cell chronic lymphocytic leukemia (B-CLL) is a common clonal B cell leukemia that is often accompanied by a multitude of immune abnormalities..[Bartik:1998]{Human}
- Our data suggests that FISH analysis of B-CLL patients provides important diagnostic, clinical, and prognostic information which may help clinicians assess the prognosis and make appropriate treatment decisions..[Beyhan:2008]{Human}
- For many decades, B cell chronic lymphocytic leukemia (B-CLL) stood out as a B cell-derived malignancy that was difficult to position within the framework of the available B cell differentiation scheme: First, the histology as well as the immunophenotype did not quite resemble that of any normal lymphocyte; second, in contrast to almost all other B cell tumor subtypes, the immunoglobulin variable region (IgV) genes of B-CLL cases could be either unmutated or somatically mutated; third, the genomic lesions observed in B-CLL were markedly distinct from those of the other major B cell malignancies, which typically exhibit balanced chromosome translocations..[Klein:2005]{Human}
- Moreover, we propose that the lack of chromosomal translocations in B-CLL may be related to their derivation from marginal zone B cells, since somatic hypermutation and Ig class switch, the processes that generate chromosome translocations in most germinal center (GC)-derived malignancies, are no longer active in marginal zone B cells. Also, we discuss similarities and differences between B-CLL and hairy cell leukemia (HCL) and suggest that also HCL may be derived from a post-GC memory or marginal zone B cell..[Klein:2005]{Human}
- Seventy-six consecutive untreated patients with B cell chronic lymphocytic leukemia (B-CLL) and classified according to Binet's staging system were studied at the clinical presentation. Several immunologic parameters (number of total and T circulating lymphocytes and their surface membrane immunoglobulin [Smlg] phenotypes and levels of serum Ig) were evaluated with the aim of identifying a biologic marker of prognostic relevance..[Baldini:1985]{Human}
- After i.v. or i.p. inoculation of 5 x 10(6) D10-1 cells, a subclone of an Epstein-Barr virus transformed human B-cell chronic lymphocytic leukemia ( CLL) line, 100% of nude mice developed solid or ascites tumors and died within 17-60 days of tumor inoculation..[Zhu:1994]{Human}
- Eight previously treated and four untreated patients with B cell chronic lymphocytic leukemia ( CLL) received 20 X 10(6) U/m2 recombinant leukocyte interferon clone A (rIFN-alpha A) intramuscularly three times a week for 8 weeks..[Schulof:1985]{Human}
- A 70-year-old woman with a 2-year history of B-cell chronic lymphocytic leukemia ( CLL) developed headache, fever, chills, and weakness..[Lee:1995]{Human}
- Blood mononuclear cells from 540 newly diagnosed, unselected patients with B-cell chronic lymphocytic leukemia ( CLL) were examined by immunofluorescence flow cytometry for a panel of surface membrane markers, including IgM and IgD, the monoclonal antibodies anti-CD3, -5, -20, -21, -22, -FMC7, and, for the final 125 patients, anti-CD23..[Geisler:1991]{Human}
- B cell chronic lymphocytic leukemia ( CLL) is a malignancy of the CD5+ B cells..[Rassenti:1993]{Human}
- ZAP-70 and CD38 expression can identify B-cell chronic lymphocytic leukemia with an inferior clinical outcome. Many groups have investigated the meaning of the expression of these two proteins and the correlation with the bad prognosis in B-CLL..[Nicolas:2007]{Human}
- The prognosis of patients with CLL is variable..[Montserrat:1997]{Human}
- In both cases of acute leukemia, the mutation was restricted to one allele and could not be detected in remission samples. Those data suggest that activation of members of the ras oncogene family, typified by K-ras, may be less important in disease pathogenesis in leukemias such as B-CLL that arise from a more committed progenitor..[Browett:1988]{Human}
- Using the interphase cytogenetic FISH approach with a disease specific set of probes, chromosome aberrations can be found in more than 80% of CLL cases. The most frequently observed abnormalities are losses of chromosomal material, with deletions in band 13q14 being the most common, followed by deletions in 11q22-q23, deletions in 17p13 and deletions in 6q21. The most common gains of chromosomal material are trisomies 12q, 8q and 3q. Translocation breakpoints, in particular involving the immunoglobulin heavy chain locus at 14q32, which are frequently observed in other types of non-Hodgkin's lymphoma, are rare events in CLL. Genes affected by common chromosome aberrations in CLL appear to be p53 in cases with 17p deletion and ataxia telangiectasia mutated (ATM), which is mutated in a subset of cases with 11q22-q23 aberrations..[Stilgenbauer:2001]{Human}
- Essential role in the pathogenesis of CLL is played by the aberrations in chromosome 17 and the p53 mutations (17p13.1). The gene p53 is defined as a tumour suppressor gene; mutations of this gene leads to a CLL characterized with rapid progression, aggressive course, poor prognosis and low survival..[Karnolsky:2001]{Human}
- Multivariate analyses showed that CD38 expression is an important prognostic factor associated with high incidence of lymph node involvement (P =.004), lower hemoglobin level (P =.001), hepatomegaly (P =.05), and high beta2M level (P =.00005)..[Ibrahim:2001]{Human}
- By using a combination oligonucleotide probe hybridization and restriction enzyme polymorphism analysis, a series of 48 cases of B-cell chronic lymphocytic leukemia were investigated for activating point mutations at codons 12, 13 and 61 of the K-ras proto-oncogene. A small series of acute leukemias (seven with acute lymphoblastic leukemia (ALL), 11 with acute myeloid leukemia (AML)) were examined in parallel..[Browett:1988]{Human}
- We conclude that the hypoproliferative anemia occurring in the course of B cell CLL is due to gradual accumulation in the marrow of T gamma lymphocytes which suppress erythroid progenitor cell growth..[Mangan:1985]{Human}
- Most samples from patients with CLL expressed the 43-kd VEGF isoform in addition to the commonly expressed 45-kd isoform..[Aguayo:2000]{Human}
- Treatment with rIFN-alpha A was associated with a depression of nonspecific and specific humoral immunity in assays employing cryopreserved autologous pretherapy CLL cells. No consistent effects were demonstrable in cytolytic assays with purified peripheral blood T cells as effector cells, including one that utilized autologous CLL target cells. rIFN-alpha A has limited antitumor activity in B cell CLL which is restricted to untreated patients with an early stage of disease..[Schulof:1985]{Human}
- These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease..[Rosenwald:2001]{Human}
- These findings contrast with a recently published study on VH5 gene expression in B CLL and contest the hypothesis that extensive somatic mutation is a common property of the VH5 genes used in this disease. Further work to define the clinical and/or phenotypic characteristics of patients with leukemia cells that express mutated versus nonmutated Ig V genes may reveal subsets of CLL that possibly differ in their cytogenesis, etiopathogenesis, and/or clinical behavior..[Rassenti:1993]{Human}
- Spontaneous apoptosis of B-CLL cells in vitro was significantly lower in samples with good prognosis cytogenetics when compared to samples with poor prognosis cytogenetics. In contrast, B-CLL cells from samples with good prognosis cytogenetics exhibited higher basal expression of molecules involved in costimulation, cellular adhesion, and antigen presentation, and induced significantly more T-cell proliferation in mixed lymphocyte cultures..[Jahrsd?rfer:2005]{Human}
- A 70-year-old woman was diagnosed with B-cell-type chronic lymphocytic leukemia (B-CLL) in May 2001. Initial white blood cell (WBC) count was 37 x 10(9)/l and most of the cells were mature small lymphocytes..[Naoko:2005]{Human}
- All these abnormalities are characteristic of the B-cell chronic lymphocytic leukemia. In the T-cell leukemia characteristic deletions are 11q22-q23, a.14q23.1, as well as the inversion inv(14)(11q32) and some rarer aberrations..[Karnolsky:2001]{Human}
- Furthermore, based on the sensitive detection of chromosome abnormalities by FISH, more accurate correlations between chromosome abnormalities and prognosis can be performed. Deletion of the TP53 gene at 17p13 have already been shown to be one of the most important independent prognostic factors for survival..[D?hner:1997]{Human}
- CD38 is a transmembrane glycoprotein expressed on the surface of leukemic cells in a significant percentage of patients with B-cell chronic lymphocytic leukemia (B-CLL). A recent study suggested that CD38 expression has prognostic value in CLL..[Ibrahim:2001]{Human}
- On analyzing the survival curves of our patients according to different Smlg phenotypes, we found that patients with only mu-type Smlg had a poorer prognosis (P less than .05) than those with mu-type plus delta-type; this difference was even more significant (P less than .01) in patients in stage A, whereas there were no statistical differences in those in stages B and C. Because the appearance of surface heavy chain of delta-type could be an expression of cell maturation, these results suggest that in B-CLL the presence of phenotypically more mature leukemic cells may correlate with better clinical prognosis, particularly in the early phase of the disease..[Baldini:1985]{Human}
- B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous malignant disease, both in terms of molecular abnormalities and clinical course. The most frequent chromosomal aberrations in B-CLL are deletions on 13q, 11q, and 17p, and trisomy 12, all of which are of prognostic significance..[Urban:2004]{Human}
- A large number of prognostic factors are available to help predict the outcome of patients who present with B-cell chronic lymphocytic leukemia (B-CLL). These include clinical stage, leukemic cell morphology, lymphocyte doubling time, the pattern of infiltration in bone marrow trephine biopsies, cytogenetic abnormalities, p53 function and serum factors such as beta-2 microglobulin..[Tryfonia:2004]{Human}
- Immunoglobulin gene analysis has also indicated the possibility of antigen selection in CLL considering the significant bias in V(H) gene usage. Intriguingly, the V(H)3-21+ group and several other CLL subsets using certain V(H) genes was recently reported to display strikingly restricted immunoglobulin gene features, in both their heavy and light chain gene rearrangements, thus further high-lighting the possible role of antigen involvement in CLL development..[Gerard:2005]{Human}
- In parallel, the accurate evaluation of the incidence of chromosome aberrations in CLL by FISH allows the correlation of genetic abnormalities with clinical disease manifestations and outcome. In particular, 17p abnormalities and deletions in 11q22-q23 have already been shown to be among the most important independent prognostic factors identifying subgroups of patients with rapid disease progression and short survival..[Stilgenbauer:2001]{Human}
- Richter syndrome (RS) is well known as a secondary high-grade lymphoma, mostly diffuse large B-cell lymphoma (DLBCL) developed in patients with B-cell chronic lymphocytic leukemia (B-CLL)..[Naoya:2003]{Human}
- This phase II study determined the efficacy and safety of alemtuzumab, a humanized anti-CD52 monoclonal antibody, delivered subcutaneously as first-line therapy, over a prolonged treatment period of 18 weeks in 41 patients with symptomatic B-cell chronic lymphocytic leukemia (B-CLL)..[Jeanette:2002]{Human}
- Allogeneic stem cell transplantation following reduced-intensity conditioning is being evaluated in patients with advanced B-cell chronic lymphocytic leukemia (B-CLL)..[Hoogendoorn:2004]{Human}
- Several authors have studied the T-lymphocyte subpopulations in B-cell chronic lymphocytic leukemia (B-CLL), but previous studies were performed after preceding enrichment procedures, which are known to cause selective losses of certain subpopulations..[Hautekeete:1987]{Human}
- In order to identify regulatory genes involved in the development of an apoptosis-resistant phenotype in patients with chemotherapy refractory B-cell chronic lymphocytic leukemia (B-CLL) expression of apoptosis-regulating genes in B-CLL cells was quantified using cDNA arrays and RT-PCR..[Alejo:2004]{Human}
- The use of telomere length and telomerase expression as new biological markers in cancer patients requires their correlation with disease prognosis. We, therefore, correlated the mean telomere length based on a telomere restriction fragment assay and the activity of telomerase measured with a telomeric repeat amplification protocol with clinical data and overall survival in 58 patients with B cell chronic lymphocytic leukemia (B-CLL)..[Bechter:1998]{Human}
- Similarly, CLL samples with high Tcl1 expression showed a decrease in DNA methylation compared with CLL samples with low Tcl1 expression. Given the previous reports of inactivating mutations of DNMT3A in acute myelogenous leukemia and myelodysplastic syndrome, our results suggest that inhibition of de novo DNA methylation may be a common oncogenic mechanism in leukemogenesis..[Alexey:2012]
- The prognostic effect of 11q deletion on survival strongly depended on the age: in patients less than 55 years old, the median survival time was significantly shorter in the deletion group (64 months v 209 months; P < .001), whereas in patients > or = 55 years old there was no significant difference (94 months v 111 months; P = .82). 11q deletions identify a new clinical subset of B-CLL characterized by extensive lymph node involvement. In younger B-CLL patients, this aberration is an important predictor of survival..[D?hner:1997]{Human}
- We report a case of classical Kaposi's sarcoma (KS) in a patient affected by B-cell chronic lymphocytic leukemia for 2 years and who had not received any antiblastic treatment..[Contu:1986]{Human}
- The patient presented a complex immunologic deficiency, revealed not only by the monoclonality of the B lymphocytes and their low degree of maturity, but also by the almost total absence of T helper lymphocytes, by the high reduction in NK activity, by the very scarce proliferative response to the polyclonal mitogens PHA, ConA and PWM, and by a complete anergy to the skin test of delayed reactivity..[Contu:1986]{Human}
- The percentage of leukemic cells expressing L-selectins (Leu-8) was high in CLL (52% of positive cases) and integrin expression (LFA-1, VLA-4, 5) was low (19 and 33%, respectively), while a reverse pattern, low Leu-8 (17%), and a high VLA-4 (77%), was observed in non-CLL cases. The expression of LFA-1 alpha-chain was variable in non-CLL cases, and the LFA-1 heterodimer was expressed on most clonal B cell in NHLs (92%)..[Csanaky:1997]{Human}
- There was no correlation between the expression of the adhesion molecules and clinical and laboratory parameters except for CD18 which was expressed on a significantly (P < 0.05) higher number of leukemic cells in CLL with more advanced stages. This study demonstrates that even closely related B cell leukemia/lymphomas have a certain well defined and strictly variable adhesion profile which is characteristic of the disease entity and therefore, the adhesion profile may offer additional information useful for differential diagnosis and study of disease pathogenesis..[Csanaky:1997]{Human}
- To clarify the cell cycle duration of stimulated cells in B cell chronic lymphocytic leukemia (B-CLL), sister chromatid differentiation (SCD) methodology was utilized..[Sadamori:1984]{Human}
- The true frequency of the CD8-positive B-cell chronic lymphocytic leukemia, any clinical implications, and the possibility of a normal subset of CD5-positive CD8-positive B cells remain to be determined..[Koelliker:1994]{Human}
- The genetic alterations underlying the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) are difficult to assess..[Stilgenbauer:1998]{Human}
- Rai and Binet staging classifications and TTM score system retained their prognostic value in this CLL population. In addition, cases fulfilling criteria of "smoldering" CLL, had a very long survival (75% survival probability at 16 years)..[Molica:1994]{Human}
- In conclusion this study confirms that prognosis of young CLL patients can be easily assessed using the current well-defined criteria. Since age is not by itself a criterion for intensifying treatment, further efforts to identify those young CLL patients who qualify for more aggressive therapy should be made..[Molica:1994]{Human}
- These results suggest that Dal B02 may be an effective carrier for the radioimmunotherapy of human B-cell CLL and other appropriate B-cell lymphomas, especially in the progressive phase of B-cell CLL, which is usually not amenable to currently available therapeutic modalities..[Zhu:1994]{Human}
- On the other hand, most cases without abnormal clones had not received treatment for relatively long periods before and after cytogenetic examination. These findings may indicate that cytogenetic results can be utilized as a parameter for treatment and prognosis in B-CLL..[Sadamori:1984]{Human}
- We have evaluated genomic aberrations by conventional cytogenetics and fluorescence in situ hybridization (FISH) analysis in a series of 57 Argentinean B-cell chronic lymphocytic leukemia (B-CLL) patients. The studies were performed on stimulated peripheral blood lymphocytes..[Christian:2003]{Human}
- However, in a subgroup of CLL patients with good prognoses or early-stage disease (Rai stages 0-II, Binet stages A,B; beta2-M </= 2.8 mg/dL), lower levels of VEGF were associated with shorter survival times..[Aguayo:2000]{Human}
- Occurrence of 13q14 deletions between D13S273 and D13S25 in B-cell chronic lymphocytic leukemia (B-CLL) suggests that the region contains a tumor suppressor gene..[van:2003]{Human}
- Results obtained suggest that the relationships between examined soluble form of TNF family proteins may influence the development of B-cell chronic lymphocytic leukemia..[Ewa:2005]{Human}
- In vitro studies were performed in two patients with B-cell chronic lymphocytic leukemia who developed pure red cell aplasia (CLL-PRCA)..[Mangan:1983]{Human}
- In this study we analyse these gene families by quantitative real-time PCR to investigate whether expression levels and the B-cell chronic lymphocytic leukemia (B-CLL) phenotype are associated..[Harikrishnan:2005]{Human}
- In this prospective study based on 106 B-cell CLL patients, we propose a combination of beta2-m and sCD23 as a strong prognostic system whose statistical significance was mainly due to an excess of deaths in the subgroup displaying increased serum levels of either beta2-m or sCD23. Multivariate survival analysis confirmed the important dominant role of such a finding, thus excluding features with a high degree of codependence (i.e. clinical stages, LDT) and including variables with low association (i.e..[Molica:1999]{Human}
- Our data indicate that good prognosis cytogenetics correlates with less spontaneous apoptosis but greater in vitro immunogenicity. These findings could have significant implications on the design of future therapeutic approaches in patients with CLL, and the likelihood of response based on cytogenetics..[Jahrsd?rfer:2005]{Human}
- The most frequent abnormality was 13q14.3 deletion, which was detected in 26 (32.9%) patients..[Beyhan:2008]{Human}
- We investigated 38 cases of B-cell chronic lymphocytic leukemia (B-CLL) for the presence of non-productive rearrangements in the S(mu) regions and defined for the first time the molecular nature of these rearrangements..[Elena:2002]{Human}
- CLL cells were cleared from blood in 95% patients in a median time of 21 days. CR or nodular PR in the bone marrow was achieved in 66% of the patients and most patients achieved this after 18 weeks of treatment. An 87% OR (29% CR) was achieved in the lymph nodes..[Jeanette:2002]{Human}
- Serum sCD23 is increased in B-CLL patients and can be used in the clinical follow-up of the disease in prediction of the tumor mass and prognosis..[Saka:2006]{Human}
- As detected by the interphase cytogenetic FISH approach, the most common chromosome abnormalities of B-CLL are deletions in band 13q14, followed by deletions in 11q22-q23, trisomy 12, deletions in 17p13, and deletions in 6q21..[Stilgenbauer:1998]{Human}
- Inactivation of TP53 in 17p13 and deletions in 11q22-q23 have already been shown to be among the most important independent prognostic factors..[Stilgenbauer:1998]{Human}
- Deletions affecting the long arm of chromosome 6 (6q) are among the most commonly observed chromosomal aberrations in lymphoid malignancies and have been identified as adverse prognostic factor in subsets of tumors..[Stilgenbauer:1999]{Human}
- For B cell chronic lymphocytic leukemia (B-CLL) conflicting data have been reported regarding the incidence and prognostic significance of 6q deletions..[Stilgenbauer:1999]{Human}
- They have become the most commonly used markers to trace loss of heterozygosity in tumors..[Urban:2004]{Human}
- On the basis of the present experiments, it is suggested that the defective colony growth of T-cell fractions in B-cell CLL may be related to the low number of OKT4-positive cells plated, which are known to be mainly responsible for the colony generation in agar culture..[Neri:1982]{Human}
- Among the promising prognostic markers is flowcytometric analysis of CD38 on the monoclonal B cells in CLL..[Boonstra:2005]{Human}
- Prolonged treatment is important for maximal bone marrow response..[Jeanette:2002]{Human}
- Short telomere length and high telomerase activity were significantly associated with a shorter median survival (P=0.02 and P <0.001), and telomerase activity was the most significant prognostic factor for overall survival in B-CLL (P <0.001)..[Bechter:1998]{Human}
- The most frequent changes observed were gains of chromosomes 3q in five cases (19%) and 17q in three cases (12%)..[Kunihiro:2005]{Human}
- A number of interesting significant interactions have been discovered, pointing to the important role of neoplastic cell microenvironment. These may in addition to insights in pathogenesis and roles of different microenvironments add to diagnosis, prognosis and treatment of B-CLL patients..[Ozren:2010]{Human}
- Our previous studies with B-cell chronic lymphocytic leukemia (B-CLL) have suggested that one of the mechanisms of nitrogen mustard (NM) drug resistance is increased repair of drug-induced damage..[Christodoulopoulos:1999]{Human}
- These results further support the concept of distinct CLL subgroups based on karyotype. Furthermore, the association of trisomy 12 and complex abnormalities with mixed-cell morphology may have implications for clonal evolution in CLL..[Kroft:1997]{Human}
- In the past two decades, significant progress has been made in CLL [4-10]. This review summarizes recent advances in the biology, diagnosis, and therapy of CLL..[Montserrat:1997]{Human}
- By FISH, the most common chromosome abnormalities are deletions of 13q followed by deletions of 11q, trisomy 12, and deletions of 17p..[D?hner:1997]{Human}
- It is important that these changes are seen not only with CpG ODN but with ODN that lack the classical CpG motif..[Bernd:2005]{Human}
- We conclude that IS ODN including CpG ODN can induce apoptosis of most B-CLL samples..[Bernd:2005]{Human}
- The elucidation of these abnormalities in the circulating non-malignant immune cells of B-CLL patients has generated important insights into the biology of the disease..[Bartik:1998]{Human}
- Forty-three of the 214 (20%) tumors exhibited 11q deletions; 11q deletions were the second most frequent chromosome aberration following 13q14 (RB1 and/or D13S25) deletions (45%); they were more frequent than trisomy 12 (15%) or deletion of 17p (TP53 gene) (10%)..[D?hner:1997]{Human}
- We used comparative genomic hybridization (CGH) to explore the cytogenetic relationship between typical and atypical B-cell CLL. Results showed a similar pattern of chromosome gains and losses detected in typical and atypical B-cell CLL, suggesting they are related disorders..[O'Connor:2000]{Human}
- We previously have shown the strong association between trisomy 12 as detected by FISH and CD11a expression in atypical B-cell CLL..[O'Connor:2000]{Human}
- At the HLA typing, the patient was DR5, as are most classical KS and/or B-CLL patients..[Contu:1986]{Human}
- We stress that immunosuppression may play an important role in the pathogenesis of both diseases and the possibility of their being conditioned by common genetic HLA-associated factors of predisposition..[Contu:1986]{Human}
- Long-distance PCRs localized the S(mu) deletions in the V(H)DJ(H) rearranged allele in most cases..[Elena:2002]{Human}
- Abnormalities of chromosomes 11 and 14 were most frequently involved in RS, but non-specific..[Naoya:2003]{Human}
- Several candidates, such as mutation of p53 gene and abnormalities of cyclin dependent kinase inhibitor, have been proposed to play an important role in the transformation of a part of B-CLL..[Naoya:2003]{Human}
- We examined the most optimal method to transform B-CLL cells into efficient antigen-presenting cells (APC) using activating cytokines, by triggering toll-like receptors (TLRs) using microbial pathogens and by CD40 stimulation with CD40L-transfected fibroblasts..[Hoogendoorn:2004]{Human}
- We hypothesise that the telomeric erosion in CLL may reflect the dominance of malignant cells with an abnormally long life span..[Sukru:2006]{Human}
- A durable anti-leukemic effect was probably important in these patients..[Mattsson:2000]{Human}
- By performing a supervised clustering of genes that most strongly discriminated between rB-CLL vs. sB-CLL a small group of genes was identified, where bfl-1 was the strongest discriminating gene (p < 0.05), with higher expression in rB-CLL..[Alejo:2004]{Human}
- Addition of CD38 to the flow cytometry antibody panel for B-CLL analysis is a relatively easy way to obtain important prognostic information..[Boonstra:2005]{Human}
- The numbers of T gamma cells infiltrating CLL marrows were increased 3, 9, and 20 times normal in Rai O through II, Rai III through IV, and CLL-aplasia groups, respectively..[Mangan:1985]{Human}
- Two of the four previously untreated patients responded with transient (90%) decreases in absolute lymphocyte counts lasting for 2 and 7 months..[Schulof:1985]{Human}
- In conclusion, bright expression of CD20 or sIg light chain is not an unusual feature in B-CLL and may not influence clinical presentation or short-term prognosis..[Tefferi:1996]{Human}
- In conclusion, CGH abnormality was associated with poor prognosis in Japanese B-CLL, and features of Japanese B-CLL, compared to chromosomal abnormalities of Western B-CLL in the literature, include a lower incidence of any abnormality in particular regarding gain of 12q, with the exception of a higher incidence of gains at 3q..[Kunihiro:2005]{Human}
- Whereas IgVH mutational status is a time consuming and demanding technique, only available in a limited number of centres, CD38 expression by flow cytometry is relatively simple and rapidly obtained in most diagnostic laboratories..[Tryfonia:2004]{Human}
- These findings suggest that p53 mutations are relatively rare in B-cell CLL, and largely predominate or may even be restricted to patients with 17p monosomy (who constitute about 5% of all B-cell CLL patients in large published series)..[Fenaux:1992]{Human}
- Recent publications have focused on two of the genes that most likely do not have a tumor suppressor role..[van:2003]{Human}
- We conclude that RFP2, c13ORF1, and a chromosome 13-specific ST13-like gene, FAM10A4, are the most likely candidates for such a type of B-CLL TSG..[van:2003]{Human}
- MDR1 was observed in 41% of CLL ZAP-70(+)CD38(+) and in 37% of CLL ZAP-70(-)CD38(-)..[Nicolas:2007]{Human}
- These findings suggest that the development of PRCA in B-cell CLL may result from suppression of CFU-E proliferation by T gamma cells..[Mangan:1983]{Human}
- Only one of six samples with acquired resistance to the nitrogen mustards had a p53 mutation suggesting that p53 mutations are not a prominent feature of acquired NM resistance in CLL..[Christodoulopoulos:1998]{Human}
- High levels of tumor necrosis factor-alpha (TNF-alpha) and soluble interleukin-2 receptor (sIL-2R) indicated advanced disease, and patients with increased levels pre- and post-SCT were also those with the most long-lasting PCR-detectable MRD post-SCT..[Mattsson:2000]{Human}
- One of the most perplexing questions regarding epigenetic modifications and leukemogenesis is the relationship with DNA methyltransferases (DNMT's)..[Harikrishnan:2005]{Human}
- Furthermore, we observed a positive correlation between HMTaseI expression levels and stage of leukemia suggesting that changes in the methylation patterns in B-CLL may represent deregulation of the epigenetic repertoire that also include the methylation dependent binding proteins, MBD2 and MeCP2..[Harikrishnan:2005]{Human}
- A remarkable finding was the detection of ICAM-1 in all CLL cases albeit the number of positive cells was significantly lower (P < 0.05) compared to non-CLL cases..[Csanaky:1997]{Human}
- Deoxynucleoside kinases are key enzymes in deoxyribonucleoside salvage, activating several clinically important chemotherapeutic drugs..[Eriksson:1994]{Human}
- The B-CLL subgroups with chromosome 11q23 deletion have been associated with aggressive disease course involving ATM deletion, extensive bulky lymphadenopathy (BLA), and inferior clinical outcome..[Avadhut:2007]{Human}
- As expected, the CLL was of B-cell lineage..[Lee:1995]{Human}
- Finally, on the basis combined increased serum levels of beta2-m and sCD23, a better stratification of low- and intermediate-risk patients could be obtained, thus allowing the formulation of a clinico-biological staging for CLL..[Molica:1999]{Human}
- Administration of 50 micrograms/mouse of Dal B02, an IgG1 (kappa) MAb directed against surface-associated antigens of human B-cell CLL, significantly prolonged the survival of D10-1-inoculated nude and SCID mice..[Zhu:1994]{Human}
- Although no objective responses were achieved in patients with fludarabine-refractory B-cell CLL, single-agent bortezomib demonstrated biologic activity..[Stefan:2006]{Human}
- Moreover no significant correlation between S(mu) deletions and prognosis was observed..[Elena:2002]{Human}
- In contrast to primary B-CLL cells as stimulator cells, these malignant APCs were capable of inducing the generation of B-CLL-reactive CD8(+) CTL lines and clones from HLA class I-matched donors..[Hoogendoorn:2004]{Human}
- Seventy-eight percent of the B-CLL patients with lymphocyte doubling time (LDT) <12 months and 24% of patients with LDT >12 months had high sCD23 levels (P = 0.008)..[Saka:2006]{Human}
- Measurement of CD38 expression by flow cytometry should become a routine test in the evaluation of patients with CLL..[Ibrahim:2001]{Human}
- Our findings imply that shortened telomeres in CLL may be reflecting the "history" of the disease and serve as an independent prognostic factor..[Sukru:2006]{Human}
- We conclude that deletions in 6q21 occur in 7% of B-CLL and identify a subgroup of patients characterized by a larger tumor mass but no inferior outcome..[Stilgenbauer:1999]{Human}
- Allelic loss of 13q14 was observed in 63.2% patients, most of them showing D13S319 and D13S25 deletion; 11% of patients showed TP53 monosomy..[Christian:2003]{Human}
- A probable adverse prognosis is suggested for this group of patients, likely related to clonal evolution..[Christian:2003]{Human}
- Serum levels of IgG, IgA and IgM were assayed simultaneously and findings were correlated with clinical stage (Rai classification)..[Hautekeete:1987]{Human}
- Results from patients in stages with equal prognosis (Rai I and II, Rai III and IV) were similar and when these results were grouped the observed differences were highly significant and clearly correlated with all prognostic groups..[Hautekeete:1987]{Human}
- We conclude that bfl-1 may be an important regulator of B-CLL apoptosis, which could contribute to disease progression and resistance to chemotherapy, and as such represent a future potential therapeutic target..[Alejo:2004]{Human}
- Although variability of CD20 and Sm Ig expression make it possible to appreciate biological heterogeneity of B-cell CLL better, however, they cannot substitute well-established clinico-hematological features in the prognostic assessment of B-CLL patients..[Molica:1998]{Human}
- CD20 intensity was classified as weak in 62% of patients, moderate in 12%, and strong in 26%..[Tefferi:1996]{Human}
- Although 3% to 5% of patients with B-cell CLL may develop higher-grade lymphoma, usually the lymphoma is of B-cell lineage and often represents a histologic manifestation of clonal evolution..[Lee:1995]{Human}
- Thus, besides clinical variables, CD23 and IgM intensity might be useful prognostic markers in the management of CD5+, B-cell CLL..[Geisler:1991]{Human}
- B-cell CLL/SLL may rarely involve the bone marrow with an interfollicular pattern..[Kim:2000]{Human}
- Tumor necrosis factor (TNF) superfamily, involving membrane receptors and ligands are important for the growth and survival of leukemic B cells..[Ewa:2005]{Human}
- By applying different algorithms, the data enabled an efficient class discrimination of the V(H)3-21+ subset based on 27 or 57 genes..[Susann:2005]{Human}
- This requires more precise research, as new anti-leukemic drugs influence the regulation of apoptosis of neoplastic B lymphocytes..[Monika:2004]{Human}
- Increased numbers of T lymphocytes were present in marrow aspirates of these patients..[Mangan:1983]{Human}
- All patients experienced acute and chronic graft-versus-host disease and responded clinically to SCT..[Mattsson:2000]{Human}
- Surprisingly, we did not observe significant changes in DNMT1 expression in B-CLL cases when compared to normal lymphocytes, regardless of whether we normalise against GAPDH or PCNA as reference standards..[Harikrishnan:2005]{Human}
|
| [17p13 and Deletions]:0.92428774
- The most frequent chromosomal aberrations in B-cell chronic lymphocytic leukemia (B-CLL) are deletions on 13q, 11q, and 17p, and trisomy 12, all of which are of prognostic significance..[Urban:2002]{Human}
- Deletions of the long arm of chromosome 11 (11q) are one of the most frequent structural chromosome aberrations in various types of lymphoproliferative disorders. However, in most conventional chromosome banding studies of B-cell chronic lymphocytic leukemia (B-CLL), 11q deletions were not identified as a frequent aberration..[D?hner:1997]{Human}
- Using the interphase cytogenetic FISH approach with a disease specific set of probes, chromosome aberrations can be found in more than 80% of CLL cases. The most frequently observed abnormalities are losses of chromosomal material, with deletions in band 13q14 being the most common, followed by deletions in 11q22-q23, deletions in 17p13 and deletions in 6q21. The most common gains of chromosomal material are trisomies 12q, 8q and 3q. Translocation breakpoints, in particular involving the immunoglobulin heavy chain locus at 14q32, which are frequently observed in other types of non-Hodgkin's lymphoma, are rare events in CLL. Genes affected by common chromosome aberrations in CLL appear to be p53 in cases with 17p deletion and ataxia telangiectasia mutated (ATM), which is mutated in a subset of cases with 11q22-q23 aberrations..[Stilgenbauer:2001]{Human}
- All these abnormalities are characteristic of the B-cell chronic lymphocytic leukemia. In the T-cell leukemia characteristic deletions are 11q22-q23, a.14q23.1, as well as the inversion inv(14)(11q32) and some rarer aberrations..[Karnolsky:2001]{Human}
- The prognostic effect of 11q deletion on survival strongly depended on the age: in patients less than 55 years old, the median survival time was significantly shorter in the deletion group (64 months v 209 months; P < .001), whereas in patients > or = 55 years old there was no significant difference (94 months v 111 months; P = .82). 11q deletions identify a new clinical subset of B-CLL characterized by extensive lymph node involvement. In younger B-CLL patients, this aberration is an important predictor of survival..[D?hner:1997]{Human}
- Occurrence of 13q14 deletions between D13S273 and D13S25 in B-cell chronic lymphocytic leukemia (B-CLL) suggests that the region contains a tumor suppressor gene..[van:2003]{Human}
- The most frequent abnormality was 13q14.3 deletion, which was detected in 26 (32.9%) patients..[Beyhan:2008]{Human}
- As detected by the interphase cytogenetic FISH approach, the most common chromosome abnormalities of B-CLL are deletions in band 13q14, followed by deletions in 11q22-q23, trisomy 12, deletions in 17p13, and deletions in 6q21..[Stilgenbauer:1998]{Human}
- Inactivation of TP53 in 17p13 and deletions in 11q22-q23 have already been shown to be among the most important independent prognostic factors..[Stilgenbauer:1998]{Human}
- For B cell chronic lymphocytic leukemia (B-CLL) conflicting data have been reported regarding the incidence and prognostic significance of 6q deletions..[Stilgenbauer:1999]{Human}
- By FISH, the most common chromosome abnormalities are deletions of 13q followed by deletions of 11q, trisomy 12, and deletions of 17p..[D?hner:1997]{Human}
- Forty-three of the 214 (20%) tumors exhibited 11q deletions; 11q deletions were the second most frequent chromosome aberration following 13q14 (RB1 and/or D13S25) deletions (45%); they were more frequent than trisomy 12 (15%) or deletion of 17p (TP53 gene) (10%)..[D?hner:1997]{Human}
- Long-distance PCRs localized the S(mu) deletions in the V(H)DJ(H) rearranged allele in most cases..[Elena:2002]{Human}
- The B-CLL subgroups with chromosome 11q23 deletion have been associated with aggressive disease course involving ATM deletion, extensive bulky lymphadenopathy (BLA), and inferior clinical outcome..[Avadhut:2007]{Human}
- Moreover no significant correlation between S(mu) deletions and prognosis was observed..[Elena:2002]{Human}
- We conclude that deletions in 6q21 occur in 7% of B-CLL and identify a subgroup of patients characterized by a larger tumor mass but no inferior outcome..[Stilgenbauer:1999]{Human}
- Allelic loss of 13q14 was observed in 63.2% patients, most of them showing D13S319 and D13S25 deletion; 11% of patients showed TP53 monosomy..[Christian:2003]{Human}
|
[Gene Mutations Status]:1.0
- The most common human leukemia is B cell chronic lymphocytic leukemia ( CLL), a malignancy of mature B cells with a characteristic clinical presentation but a variable clinical course. The rearranged immunoglobulin (Ig) genes of CLL cells may be either germ-line in sequence or somatically mutated. Lack of Ig mutations defined a distinctly worse prognostic group of CLL patients raising the possibility that CLL comprises two distinct diseases. Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression "signature," irrespective of Ig mutational status, suggesting that CLL cases share a common mechanism of transformation and/or cell of origin..[Rosenwald:2001]{Human}
- B-cell chronic lymphocytic leukemia ( CLL) is a clinically heterogeneous disease with many patients surviving for decades with minimal or no treatment, whereas others succumb rapidly to their disease despite therapy. In recent years, new molecular prognostic factors have emerged in CLL that have significantly improved the subgrouping of the disease. One of the most important molecular predictors, the immunoglobulin V(H) gene mutation status, divides CLL into two prognostic groups, depending on the presence or absence of somatic hypermutation, where unmutated V(H) genes are associated with considerably worse prognosis than mutated V(H) genes. An exception to this appears to be CLL patients utilizing the V(H)3-21 gene as they have poor outcome irrespective of mutation status..[Gerard:2005]{Human}
- The usage of the immunoglobulin (Ig) V(H)3-21 gene is associated with poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) despite V(H) gene mutation status..[Susann:2005]{Human}
- Mutations of exons 5 to 8 of the p53 gene were looked for in 39 cases of B-cell chronic lymphocytic leukemia ( CLL) using polymerase chain reaction single-strand conformation polymorphism analysis and DNA sequencing..[Fenaux:1992]{Human}
- However, a recent report indicated that VH251, one of three VH genes belonging to the VH5 subgroup (e.g., VH251, VH32, and VH15), not only is frequently rearranged in this disease, but also has extensive and selective mutations when expressed by CLL B cells. The extent and nature of these mutations contrasts markedly from the low level of mutations noted in VH5 genes used by normal B cells or other Ig V genes found expressed in CLL. To determine whether this difference reflects a unique property of VH251 or a previously unrecognized subgroup of CLL, we examined for VH5 Ig gene rearrangements in leukemia cells from 68 patients that satisfied clinical and diagnostic criteria for CD5+ B cell CLL. Southern blot hybridization studies with probes for VH251 and the JH locus revealed that only 7 (10%) of the 68 monoclonal CLL cell populations had undergone Ig gene rearrangement involving VH5 genes. Two (3%) were found to have functionally rearranged VH5 genes that shared > or = 98% sequence homology with 5-2R1, a VH251 gene isolated from a pre-B cell acute lymphocytic leukemia. The other five CLL (7%) had functionally rearranged VH5 genes that each shared > or = 99% nucleic acid sequence homology with a germline VH32 isolated from human sperm DNA..[Rassenti:1993]{Human}
- For many decades, B cell chronic lymphocytic leukemia (B-CLL) stood out as a B cell-derived malignancy that was difficult to position within the framework of the available B cell differentiation scheme: First, the histology as well as the immunophenotype did not quite resemble that of any normal lymphocyte; second, in contrast to almost all other B cell tumor subtypes, the immunoglobulin variable region (IgV) genes of B-CLL cases could be either unmutated or somatically mutated; third, the genomic lesions observed in B-CLL were markedly distinct from those of the other major B cell malignancies, which typically exhibit balanced chromosome translocations..[Klein:2005]{Human}
- Essential role in the pathogenesis of CLL is played by the aberrations in chromosome 17 and the p53 mutations (17p13.1). The gene p53 is defined as a tumour suppressor gene; mutations of this gene leads to a CLL characterized with rapid progression, aggressive course, poor prognosis and low survival..[Karnolsky:2001]{Human}
- These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease..[Rosenwald:2001]{Human}
- These findings contrast with a recently published study on VH5 gene expression in B CLL and contest the hypothesis that extensive somatic mutation is a common property of the VH5 genes used in this disease. Further work to define the clinical and/or phenotypic characteristics of patients with leukemia cells that express mutated versus nonmutated Ig V genes may reveal subsets of CLL that possibly differ in their cytogenesis, etiopathogenesis, and/or clinical behavior..[Rassenti:1993]{Human}
- Immunoglobulin gene analysis has also indicated the possibility of antigen selection in CLL considering the significant bias in V(H) gene usage. Intriguingly, the V(H)3-21+ group and several other CLL subsets using certain V(H) genes was recently reported to display strikingly restricted immunoglobulin gene features, in both their heavy and light chain gene rearrangements, thus further high-lighting the possible role of antigen involvement in CLL development..[Gerard:2005]{Human}
- In order to identify regulatory genes involved in the development of an apoptosis-resistant phenotype in patients with chemotherapy refractory B-cell chronic lymphocytic leukemia (B-CLL) expression of apoptosis-regulating genes in B-CLL cells was quantified using cDNA arrays and RT-PCR..[Alejo:2004]{Human}
- Several candidates, such as mutation of p53 gene and abnormalities of cyclin dependent kinase inhibitor, have been proposed to play an important role in the transformation of a part of B-CLL..[Naoya:2003]{Human}
- By performing a supervised clustering of genes that most strongly discriminated between rB-CLL vs. sB-CLL a small group of genes was identified, where bfl-1 was the strongest discriminating gene (p < 0.05), with higher expression in rB-CLL..[Alejo:2004]{Human}
- We conclude that RFP2, c13ORF1, and a chromosome 13-specific ST13-like gene, FAM10A4, are the most likely candidates for such a type of B-CLL TSG..[van:2003]{Human}
- Only one of six samples with acquired resistance to the nitrogen mustards had a p53 mutation suggesting that p53 mutations are not a prominent feature of acquired NM resistance in CLL..[Christodoulopoulos:1998]{Human}
|
[CLL Cases]:0.6392373
- Peripheral blood lymphocyte morphology and karyotype were correlated across the spectrum of cytogenetic abnormalities in 78 previously karyotyped cases of B-cell chronic lymphocytic leukemia ( CLL). Cases were classified according to French-American-British morphologic criteria as typical CLL or CLL, mixed-cell type; the latter category was divided into CLL with a mixture of small and large cells and CLL with increased prolymphocytes ( CLL/PL)..[Kroft:1997]{Human}
- Fifty-three patients affected with B-cell chronic lymphocytic leukemia ( CLL) younger than 50 years and observed in two hematological institutions have been retrospectively evaluated in order to verify whether this disease has different clinico-hematological features at presentation and different prognosis as compared to older cases. In our experience young cases with B-CLL diagnosis, confirmed by immunophenotype in 90.5% of patients, accounted for 7.1% of the whole CLL population..[Molica:1994]{Human}
- The coexistence of acute myeloid leukemia and chronic lymphocytic leukemia in the same patient is rare. The majority of the cases correspond to patients that developed acute leukemia during the evolutionary course of a chronic lymphatic leukemia following treatment with chemotherapy drugs. We report a case of acute myelomonocytic leukemia concurrent with untreated B-cell chronic lymphocytic leukemia in which the use of flow cytometry analysis with a large panel of monoclonal antibodies, allowed the demonstration of different pathological populations and determine immunophenotyping patterns. Published cases of simultaneous chronic lymphocytic leukemia and acute leukemia are reviewed..[Viviana:2010]{Human}
- The chromosome constitutions of stimulated lymphocytes in 21 untreated cases with B-cell chronic lymphocytic leukemia (B-CLL) were examined..[Sadamori:1984]{Human}
- Mutations of exons 5 to 8 of the p53 gene were looked for in 39 cases of B-cell chronic lymphocytic leukemia ( CLL) using polymerase chain reaction single-strand conformation polymorphism analysis and DNA sequencing..[Fenaux:1992]{Human}
- In both cases of acute leukemia, the mutation was restricted to one allele and could not be detected in remission samples. Those data suggest that activation of members of the ras oncogene family, typified by K-ras, may be less important in disease pathogenesis in leukemias such as B-CLL that arise from a more committed progenitor..[Browett:1988]{Human}
- Using the interphase cytogenetic FISH approach with a disease specific set of probes, chromosome aberrations can be found in more than 80% of CLL cases. The most frequently observed abnormalities are losses of chromosomal material, with deletions in band 13q14 being the most common, followed by deletions in 11q22-q23, deletions in 17p13 and deletions in 6q21. The most common gains of chromosomal material are trisomies 12q, 8q and 3q. Translocation breakpoints, in particular involving the immunoglobulin heavy chain locus at 14q32, which are frequently observed in other types of non-Hodgkin's lymphoma, are rare events in CLL. Genes affected by common chromosome aberrations in CLL appear to be p53 in cases with 17p deletion and ataxia telangiectasia mutated (ATM), which is mutated in a subset of cases with 11q22-q23 aberrations..[Stilgenbauer:2001]{Human}
- We report a case of classical Kaposi's sarcoma (KS) in a patient affected by B-cell chronic lymphocytic leukemia for 2 years and who had not received any antiblastic treatment..[Contu:1986]{Human}
- The percentage of leukemic cells expressing L-selectins (Leu-8) was high in CLL (52% of positive cases) and integrin expression (LFA-1, VLA-4, 5) was low (19 and 33%, respectively), while a reverse pattern, low Leu-8 (17%), and a high VLA-4 (77%), was observed in non-CLL cases. The expression of LFA-1 alpha-chain was variable in non-CLL cases, and the LFA-1 heterodimer was expressed on most clonal B cell in NHLs (92%)..[Csanaky:1997]{Human}
- The most frequent changes observed were gains of chromosomes 3q in five cases (19%) and 17q in three cases (12%)..[Kunihiro:2005]{Human}
- Long-distance PCRs localized the S(mu) deletions in the V(H)DJ(H) rearranged allele in most cases..[Elena:2002]{Human}
- A remarkable finding was the detection of ICAM-1 in all CLL cases albeit the number of positive cells was significantly lower (P < 0.05) compared to non-CLL cases..[Csanaky:1997]{Human}
- Surprisingly, we did not observe significant changes in DNMT1 expression in B-CLL cases when compared to normal lymphocytes, regardless of whether we normalise against GAPDH or PCNA as reference standards..[Harikrishnan:2005]{Human}
|
[Cd38 Expression]:0.4786939
- ZAP-70 and CD38 expression can identify B-cell chronic lymphocytic leukemia with an inferior clinical outcome. Many groups have investigated the meaning of the expression of these two proteins and the correlation with the bad prognosis in B-CLL..[Nicolas:2007]{Human}
- Multivariate analyses showed that CD38 expression is an important prognostic factor associated with high incidence of lymph node involvement (P =.004), lower hemoglobin level (P =.001), hepatomegaly (P =.05), and high beta2M level (P =.00005)..[Ibrahim:2001]{Human}
- Most samples from patients with CLL expressed the 43-kd VEGF isoform in addition to the commonly expressed 45-kd isoform..[Aguayo:2000]{Human}
- CD38 is a transmembrane glycoprotein expressed on the surface of leukemic cells in a significant percentage of patients with B-cell chronic lymphocytic leukemia (B-CLL). A recent study suggested that CD38 expression has prognostic value in CLL..[Ibrahim:2001]{Human}
- Among the promising prognostic markers is flowcytometric analysis of CD38 on the monoclonal B cells in CLL..[Boonstra:2005]{Human}
- Addition of CD38 to the flow cytometry antibody panel for B-CLL analysis is a relatively easy way to obtain important prognostic information..[Boonstra:2005]{Human}
- Whereas IgVH mutational status is a time consuming and demanding technique, only available in a limited number of centres, CD38 expression by flow cytometry is relatively simple and rapidly obtained in most diagnostic laboratories..[Tryfonia:2004]{Human}
- MDR1 was observed in 41% of CLL ZAP-70(+)CD38(+) and in 37% of CLL ZAP-70(-)CD38(-)..[Nicolas:2007]{Human}
- Measurement of CD38 expression by flow cytometry should become a routine test in the evaluation of patients with CLL..[Ibrahim:2001]{Human}
|
[Observed Chromosome]:0.46053493
- This well-documented acquired anomaly is one of the most specific numerical chromosome alterations to occur in human hematological malignancies. We have cytogenetically characterized bone marrow and peripheral blood cells from a patient with B-cell chronic lymphocytic leukemia ( CLL) having a unique acquired translocation involving chromosomes 6 and 12, t(6;12) (p21.3;q13), which implicates band 12q13 as the site of the gene(s) important in this lymphoproliferative B-cell disorder. Aneuploidy, in the form of trisomy of chromosome 12, is not a requirement for neoplastic transformation in B-cell CLL, but gene rearrangement (present case) or nondisjunctional acquisition of additional copies of defective genes on chromosome 12 at band q13 may be involved in the genesis or progression of this disorder..[Stock:1999]{Human}
- The most frequent chromosome aberrations in B cell chronic lymphocytic leukemia (B-CLL) detected by conventional chromosome banding analysis are trisomy 12 followed by structural abnormalities of the long arms of chromosomes 13, 14, and 11. Complex karyotypes, trisomy 12, and a '14q+' abnormality have been associated with inferior prognosis, whereas aberrations of 13q have been found in patients with a favorable outcome..[D?hner:1997]{Human}
- Deletions of the long arm of chromosome 11 (11q) are one of the most frequent structural chromosome aberrations in various types of lymphoproliferative disorders. However, in most conventional chromosome banding studies of B-cell chronic lymphocytic leukemia (B-CLL), 11q deletions were not identified as a frequent aberration..[D?hner:1997]{Human}
- Chromosomal abnormalities in B-cell chronic lymphocytic leukemia (B-CLL) have been shown to correlate with prognosis..[Jahrsd?rfer:2005]{Human}
- For many decades, B cell chronic lymphocytic leukemia (B-CLL) stood out as a B cell-derived malignancy that was difficult to position within the framework of the available B cell differentiation scheme: First, the histology as well as the immunophenotype did not quite resemble that of any normal lymphocyte; second, in contrast to almost all other B cell tumor subtypes, the immunoglobulin variable region (IgV) genes of B-CLL cases could be either unmutated or somatically mutated; third, the genomic lesions observed in B-CLL were markedly distinct from those of the other major B cell malignancies, which typically exhibit balanced chromosome translocations..[Klein:2005]{Human}
- Using the interphase cytogenetic FISH approach with a disease specific set of probes, chromosome aberrations can be found in more than 80% of CLL cases. The most frequently observed abnormalities are losses of chromosomal material, with deletions in band 13q14 being the most common, followed by deletions in 11q22-q23, deletions in 17p13 and deletions in 6q21. The most common gains of chromosomal material are trisomies 12q, 8q and 3q. Translocation breakpoints, in particular involving the immunoglobulin heavy chain locus at 14q32, which are frequently observed in other types of non-Hodgkin's lymphoma, are rare events in CLL. Genes affected by common chromosome aberrations in CLL appear to be p53 in cases with 17p deletion and ataxia telangiectasia mutated (ATM), which is mutated in a subset of cases with 11q22-q23 aberrations..[Stilgenbauer:2001]{Human}
- Furthermore, based on the sensitive detection of chromosome abnormalities by FISH, more accurate correlations between chromosome abnormalities and prognosis can be performed. Deletion of the TP53 gene at 17p13 have already been shown to be one of the most important independent prognostic factors for survival..[D?hner:1997]{Human}
- Deletions affecting the long arm of chromosome 6 (6q) are among the most commonly observed chromosomal aberrations in lymphoid malignancies and have been identified as adverse prognostic factor in subsets of tumors..[Stilgenbauer:1999]{Human}
- The most frequent changes observed were gains of chromosomes 3q in five cases (19%) and 17q in three cases (12%)..[Kunihiro:2005]{Human}
- Abnormalities of chromosomes 11 and 14 were most frequently involved in RS, but non-specific..[Naoya:2003]{Human}
- We conclude that RFP2, c13ORF1, and a chromosome 13-specific ST13-like gene, FAM10A4, are the most likely candidates for such a type of B-CLL TSG..[van:2003]{Human}
- MDR1 was observed in 41% of CLL ZAP-70(+)CD38(+) and in 37% of CLL ZAP-70(-)CD38(-)..[Nicolas:2007]{Human}
- Moreover no significant correlation between S(mu) deletions and prognosis was observed..[Elena:2002]{Human}
- Allelic loss of 13q14 was observed in 63.2% patients, most of them showing D13S319 and D13S25 deletion; 11% of patients showed TP53 monosomy..[Christian:2003]{Human}
- Surprisingly, we did not observe significant changes in DNMT1 expression in B-CLL cases when compared to normal lymphocytes, regardless of whether we normalise against GAPDH or PCNA as reference standards..[Harikrishnan:2005]{Human}
|
[Involving the Bone Marrow]:0.4107828
- B-cell chronic lymphocytic leukemia (B-CLL) is characterized by highly variable distribution of tumor mass between peripheral blood, bone marrow and lymphoid organs which is important for staging, classification and prognosis. These clinical findings with novel data about importance of B-cell receptor and its stimulation with the support of microenvironment indicate important role of tissues (lymphoid organs and bone marrow) in the pathogenesis of B-CLL. Here is presented the novel approach of simultaneous characterization of B-CLL cells form peripheral blood, bone marrow and lymph nodes by flow cytometry and immunocytochemistry, defining inter- and intraclonal diversity with respect to various molecules..[Ozren:2010]{Human}
- This well-documented acquired anomaly is one of the most specific numerical chromosome alterations to occur in human hematological malignancies. We have cytogenetically characterized bone marrow and peripheral blood cells from a patient with B-cell chronic lymphocytic leukemia ( CLL) having a unique acquired translocation involving chromosomes 6 and 12, t(6;12) (p21.3;q13), which implicates band 12q13 as the site of the gene(s) important in this lymphoproliferative B-cell disorder. Aneuploidy, in the form of trisomy of chromosome 12, is not a requirement for neoplastic transformation in B-cell CLL, but gene rearrangement (present case) or nondisjunctional acquisition of additional copies of defective genes on chromosome 12 at band q13 may be involved in the genesis or progression of this disorder..[Stock:1999]{Human}
- Soluble CD23 (sCD23) and beta-2 microglobulin (beta2-m) are reliable prognostic parameters in B-cell chronic lymphocytic leukemia ( CLL); however, their merit over well-established clinical variables such as clinical stages, bone marrow (BM) histology and lymphocyte doubling time (LDT) remains to be defined..[Molica:1999]{Human}
- B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma ( CLL/SLL) may involve the bone marrow in nodular, interstitial, diffuse, or mixed patterns. However, B-cell CLL/SLL associated with large reactive germinal centers (the so-called interfollicular pattern) involving the bone marrow is not reported. We describe 2 examples of B-cell CLL/SLL that subtotally replaced the bone marrow with an interfollicular pattern..[Kim:2000]{Human}
- CLL cells were cleared from blood in 95% patients in a median time of 21 days. CR or nodular PR in the bone marrow was achieved in 66% of the patients and most patients achieved this after 18 weeks of treatment. An 87% OR (29% CR) was achieved in the lymph nodes..[Jeanette:2002]{Human}
- Prolonged treatment is important for maximal bone marrow response..[Jeanette:2002]{Human}
- Abnormalities of chromosomes 11 and 14 were most frequently involved in RS, but non-specific..[Naoya:2003]{Human}
- B-cell CLL/SLL may rarely involve the bone marrow with an interfollicular pattern..[Kim:2000]{Human}
- Tumor necrosis factor (TNF) superfamily, involving membrane receptors and ligands are important for the growth and survival of leukemic B cells..[Ewa:2005]{Human}
|
[B-cell Chronic Lymphocytic Leukemia B-CLL]:0.39874673
- B-cell chronic lymphocytic leukemia (B-CLL) is the most common B-cell leukemia among older populations in Western countries..[Avadhut:2007]{Human}
- B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in Western countries and results from the accumulation of B-lymphocytes which are functionally abnormal and predominantly non-cycling in vivo. Consequently, it is important to understand why B-CLL cells accumulate in GO phase. Since TGF-beta is an important negative regulator of the immune system, a loss of responsiveness to this factor might provide a selective advantage to B-CLL cells..[Lagneaux:1998]{Human}
- B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in Westerners..[Kunihiro:2005]{Human}
- In B-cell chronic lymphocytic leukemia (B-CLL) the Rai and Binet staging criteria are not always able to accurately predict the prognosis of each patient..[Boonstra:2005]{Human}
- Chromosomal abnormalities in B-cell chronic lymphocytic leukemia (B-CLL) have been shown to correlate with prognosis..[Jahrsd?rfer:2005]{Human}
- Richter syndrome (RS) is well known as a secondary high-grade lymphoma, mostly diffuse large B-cell lymphoma (DLBCL) developed in patients with B-cell chronic lymphocytic leukemia (B-CLL)..[Naoya:2003]{Human}
- In order to identify regulatory genes involved in the development of an apoptosis-resistant phenotype in patients with chemotherapy refractory B-cell chronic lymphocytic leukemia (B-CLL) expression of apoptosis-regulating genes in B-CLL cells was quantified using cDNA arrays and RT-PCR..[Alejo:2004]{Human}
- The genetic alterations underlying the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) are difficult to assess..[Stilgenbauer:1998]{Human}
- Occurrence of 13q14 deletions between D13S273 and D13S25 in B-cell chronic lymphocytic leukemia (B-CLL) suggests that the region contains a tumor suppressor gene..[van:2003]{Human}
- At the HLA typing, the patient was DR5, as are most classical KS and/or B-CLL patients..[Contu:1986]{Human}
- As expected, the CLL was of B-cell lineage..[Lee:1995]{Human}
|
[B-cell Lymphoma]:0.3720734
- The expression of a series of adhesion receptors: L-selectins (CD62L): Leu-8, several integrins (LFA-1: CD11a/CD18, VLA-4: CD49d/CD29 and VLA-5: CD49e/CD29), ICAM-1(CD54) and the 'homing receptor' (CD44) were investigated by a dual color flow cytometry in 56 cases of B cell disorders namely, 39 chronic lymphocytic leukemias ( CLL), four hairy cell leukemia (HCL), seven splenic lymphoma with villous lymphocytes (SLVL) and six other non-Hodgkin's lymphoma (NHL)..[Csanaky:1997]{Human}
- B-cell chronic lymphocytic leukemia ( CLL) is the most common human leukemia. Deregulation of the T-cell leukemia/lymphoma 1 oncogene (TCL1) in mouse B cells causes a CD5(+) leukemia similar to aggressive human CLL..[Alexey:2012]
- Granulomatous cutaneous reactions are well described in association with T-cell non-Hodgkin lymphoma and Hodgkin lymphoma, but are rarely seen in association with B-cell non-Hodgkin lymphoma or leukemia. We report a case of a 65-year-old woman with B-cell chronic lymphocytic leukemia ( CLL)/small lymphocytic lymphoma (SLL) who presented with multiple, tender, firm pink papules on the face, upper trunk and upper extremities 6 years after diagnosis of CLL. Biopsy revealed both palisading granulomatous dermatitis consistent with actinic granuloma and a dense perivascular lymphocytic infiltrate consistent with the patient's known history of leukemia. This is an unusual manifestation of cutaneous B-cell CLL that is rarely seen..[Julia:2012]
- One of the main reasons for interest in these molecules is that they may play a determining role in neoplastic transformation and diffusion; in particular, in lymphoproliferative syndromes, a lack of cell adhesiveness or an abnormal adhesion pattern in neoplastic lymphocytes may free these cells from regulation, thus contributing towards the development of leukemia and/or lymphoma. Studies of VLA expression in B-cell leukemia/lymphomas show a modulation of VLA3 and VLA4 reactivity. The most interesting element is the identification of a VLA3/VLA4 pattern associated with B-cell chronic lymphocytic leukemia (B-CLL) characterised by a reduced expression of VLA4 and the constant expression of VLA3..[Baldini:1994]{Human}
- Richter syndrome (RS) is well known as a secondary high-grade lymphoma, mostly diffuse large B-cell lymphoma (DLBCL) developed in patients with B-cell chronic lymphocytic leukemia (B-CLL)..[Naoya:2003]{Human}
- These results suggest that Dal B02 may be an effective carrier for the radioimmunotherapy of human B-cell CLL and other appropriate B-cell lymphomas, especially in the progressive phase of B-cell CLL, which is usually not amenable to currently available therapeutic modalities..[Zhu:1994]{Human}
- As expected, the CLL was of B-cell lineage..[Lee:1995]{Human}
- Although 3% to 5% of patients with B-cell CLL may develop higher-grade lymphoma, usually the lymphoma is of B-cell lineage and often represents a histologic manifestation of clonal evolution..[Lee:1995]{Human}
|
[CLL Patients]:0.33949304
- Following allogeneic stem cell transplantation (SCT), we studied the presence of donor and recipient derived cells within the CD19+ B cell fraction, in patients with B cell chronic lymphocytic leukemia ( CLL)..[Mattsson:2000]{Human}
- The prognosis of patients with CLL is variable..[Montserrat:1997]{Human}
- These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease..[Rosenwald:2001]{Human}
- In conclusion this study confirms that prognosis of young CLL patients can be easily assessed using the current well-defined criteria. Since age is not by itself a criterion for intensifying treatment, further efforts to identify those young CLL patients who qualify for more aggressive therapy should be made..[Molica:1994]{Human}
- CLL cells were cleared from blood in 95% patients in a median time of 21 days. CR or nodular PR in the bone marrow was achieved in 66% of the patients and most patients achieved this after 18 weeks of treatment. An 87% OR (29% CR) was achieved in the lymph nodes..[Jeanette:2002]{Human}
- The elucidation of these abnormalities in the circulating non-malignant immune cells of B-CLL patients has generated important insights into the biology of the disease..[Bartik:1998]{Human}
- At the HLA typing, the patient was DR5, as are most classical KS and/or B-CLL patients..[Contu:1986]{Human}
- A durable anti-leukemic effect was probably important in these patients..[Mattsson:2000]{Human}
- All patients experienced acute and chronic graft-versus-host disease and responded clinically to SCT..[Mattsson:2000]{Human}
|
[Rai and Binet Stages]:0.3218035
- To define further the role of marrow T suppressor lymphocytes in the pathogenesis of the hypoproliferative anemia in all Rai clinical stages of B cell chronic lymphocytic leukemia ( CLL), marrow erythroid progenitor cell (CFU-E and BFU-E) frequency, marrow T gamma lymphocyte frequency per 1,000 nucleated marrow cells, and T cell-erythroid progenitor cell interactions were examined in 30 CLL patients and normal control subjects..[Mangan:1985]{Human}
- Recent reports of successfully completed cytogenetic studies using polyclonal B-cell activators demonstrate that trisomy-12 and 14 q+ are the most frequently observed chromosomal abnormalities in B-cell chronic lymphocytic leukemia ( CLL). It appears that when trisomy-12 is accompanied by yet another abnormality, the prognosis of patients is uniformly poor. Patients in early stages of CLL retain delayed hypersensitivity reactivity, while those in advanced stages are usually anergic. The lymphocytes from venous blood of patients with CLL appear to retain at least some ability to respond to stimulation with mitogens in early stages, whereas in advanced stages they show no response to mitogens. Serum immunoglobulin levels are normal in the early (0 and I) stages, are markedly decreased in the advanced (III and IV) stages, and are somewhat between these extremes in the intermediate (II) stage of CLL. Prolymphocytic leukemia and prolymphocytoid transformation of CLL are indicators of poor prognosis, while a morphological variant characterized by large granular lymphocyte is associated with good prognosis. At this time it is not possible to ascribe strong prognostic significance to phenotypic features of lymphocytes in B-CLL; however, studies currently in progress may soon provide important insights on this subject..[Rai:1987]{Human}
- In B-cell chronic lymphocytic leukemia (B-CLL) the Rai and Binet staging criteria are not always able to accurately predict the prognosis of each patient..[Boonstra:2005]{Human}
- Rai and Binet staging classifications and TTM score system retained their prognostic value in this CLL population. In addition, cases fulfilling criteria of "smoldering" CLL, had a very long survival (75% survival probability at 16 years)..[Molica:1994]{Human}
- However, in a subgroup of CLL patients with good prognoses or early-stage disease (Rai stages 0-II, Binet stages A,B; beta2-M </= 2.8 mg/dL), lower levels of VEGF were associated with shorter survival times..[Aguayo:2000]{Human}
- The numbers of T gamma cells infiltrating CLL marrows were increased 3, 9, and 20 times normal in Rai O through II, Rai III through IV, and CLL-aplasia groups, respectively..[Mangan:1985]{Human}
- Serum levels of IgG, IgA and IgM were assayed simultaneously and findings were correlated with clinical stage (Rai classification)..[Hautekeete:1987]{Human}
- Results from patients in stages with equal prognosis (Rai I and II, Rai III and IV) were similar and when these results were grouped the observed differences were highly significant and clearly correlated with all prognostic groups..[Hautekeete:1987]{Human}
|
[Previously Untreated Patients]:0.3108201
- The chromosome constitutions of stimulated lymphocytes in 21 untreated cases with B-cell chronic lymphocytic leukemia (B-CLL) were examined..[Sadamori:1984]{Human}
- T-lymphocyte colony formation in agar culture was investigated in 20 untreated B-cell Chronic Lymphocytic Leukemia ( CLL) patients in stage O. As compared to the controls, colony growth was very poor when unseparated peripheral-blood lymphocytes from CLL-patients were seeded. The number of colonies was greatly higher when T-cell enriched fractions from CLL were plated; however, they failed to reach the normal range even in this experimental condition..[Neri:1982]{Human}
- In a prospective study, peripheral lymphocytes of 93 previously untreated patients with B-cell chronic lymphocytic leukemia (B-CLL) were evaluated with flow cytometry for the intensity of CD20 and surface immunoglobulin (sIg) light-chain (LC) expression..[Tefferi:1996]{Human}
- Eight previously treated and four untreated patients with B cell chronic lymphocytic leukemia ( CLL) received 20 X 10(6) U/m2 recombinant leukocyte interferon clone A (rIFN-alpha A) intramuscularly three times a week for 8 weeks..[Schulof:1985]{Human}
- Treatment with rIFN-alpha A was associated with a depression of nonspecific and specific humoral immunity in assays employing cryopreserved autologous pretherapy CLL cells. No consistent effects were demonstrable in cytolytic assays with purified peripheral blood T cells as effector cells, including one that utilized autologous CLL target cells. rIFN-alpha A has limited antitumor activity in B cell CLL which is restricted to untreated patients with an early stage of disease..[Schulof:1985]{Human}
- Our previous studies with B-cell chronic lymphocytic leukemia (B-CLL) have suggested that one of the mechanisms of nitrogen mustard (NM) drug resistance is increased repair of drug-induced damage..[Christodoulopoulos:1999]{Human}
- We previously have shown the strong association between trisomy 12 as detected by FISH and CD11a expression in atypical B-cell CLL..[O'Connor:2000]{Human}
- Two of the four previously untreated patients responded with transient (90%) decreases in absolute lymphocyte counts lasting for 2 and 7 months..[Schulof:1985]{Human}
|
[Clinical Variable]:0.30541217
- Soluble CD23 (sCD23) and beta-2 microglobulin (beta2-m) are reliable prognostic parameters in B-cell chronic lymphocytic leukemia ( CLL); however, their merit over well-established clinical variables such as clinical stages, bone marrow (BM) histology and lymphocyte doubling time (LDT) remains to be defined..[Molica:1999]{Human}
- The prognosis of patients with CLL is variable..[Montserrat:1997]{Human}
- These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease..[Rosenwald:2001]{Human}
- In this prospective study based on 106 B-cell CLL patients, we propose a combination of beta2-m and sCD23 as a strong prognostic system whose statistical significance was mainly due to an excess of deaths in the subgroup displaying increased serum levels of either beta2-m or sCD23. Multivariate survival analysis confirmed the important dominant role of such a finding, thus excluding features with a high degree of codependence (i.e. clinical stages, LDT) and including variables with low association (i.e..[Molica:1999]{Human}
- Although variability of CD20 and Sm Ig expression make it possible to appreciate biological heterogeneity of B-cell CLL better, however, they cannot substitute well-established clinico-hematological features in the prognostic assessment of B-CLL patients..[Molica:1998]{Human}
- Thus, besides clinical variables, CD23 and IgM intensity might be useful prognostic markers in the management of CD5+, B-cell CLL..[Geisler:1991]{Human}
- All patients experienced acute and chronic graft-versus-host disease and responded clinically to SCT..[Mattsson:2000]{Human}
|
[Role in the Pathogenesis]:0.2904011
- To define further the role of marrow T suppressor lymphocytes in the pathogenesis of the hypoproliferative anemia in all Rai clinical stages of B cell chronic lymphocytic leukemia ( CLL), marrow erythroid progenitor cell (CFU-E and BFU-E) frequency, marrow T gamma lymphocyte frequency per 1,000 nucleated marrow cells, and T cell-erythroid progenitor cell interactions were examined in 30 CLL patients and normal control subjects..[Mangan:1985]{Human}
- B-cell chronic lymphocytic leukemia (B-CLL) is characterized by highly variable distribution of tumor mass between peripheral blood, bone marrow and lymphoid organs which is important for staging, classification and prognosis. These clinical findings with novel data about importance of B-cell receptor and its stimulation with the support of microenvironment indicate important role of tissues (lymphoid organs and bone marrow) in the pathogenesis of B-CLL. Here is presented the novel approach of simultaneous characterization of B-CLL cells form peripheral blood, bone marrow and lymph nodes by flow cytometry and immunocytochemistry, defining inter- and intraclonal diversity with respect to various molecules..[Ozren:2010]{Human}
- We propose that lymph node stromal cells play an important role in the differentiation of B cells through direct contact and that HN cells will be useful for investigating the differentiation pathway of chronic B cell leukemia cells..[Takeuchi:1995]{Human}
- In both cases of acute leukemia, the mutation was restricted to one allele and could not be detected in remission samples. Those data suggest that activation of members of the ras oncogene family, typified by K-ras, may be less important in disease pathogenesis in leukemias such as B-CLL that arise from a more committed progenitor..[Browett:1988]{Human}
- Essential role in the pathogenesis of CLL is played by the aberrations in chromosome 17 and the p53 mutations (17p13.1). The gene p53 is defined as a tumour suppressor gene; mutations of this gene leads to a CLL characterized with rapid progression, aggressive course, poor prognosis and low survival..[Karnolsky:2001]{Human}
- The genetic alterations underlying the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) are difficult to assess..[Stilgenbauer:1998]{Human}
- A number of interesting significant interactions have been discovered, pointing to the important role of neoplastic cell microenvironment. These may in addition to insights in pathogenesis and roles of different microenvironments add to diagnosis, prognosis and treatment of B-CLL patients..[Ozren:2010]{Human}
- We stress that immunosuppression may play an important role in the pathogenesis of both diseases and the possibility of their being conditioned by common genetic HLA-associated factors of predisposition..[Contu:1986]{Human}
- Several candidates, such as mutation of p53 gene and abnormalities of cyclin dependent kinase inhibitor, have been proposed to play an important role in the transformation of a part of B-CLL..[Naoya:2003]{Human}
- Recent publications have focused on two of the genes that most likely do not have a tumor suppressor role..[van:2003]{Human}
|
[Results Suggest]:0.2860124
- Similarly, CLL samples with high Tcl1 expression showed a decrease in DNA methylation compared with CLL samples with low Tcl1 expression. Given the previous reports of inactivating mutations of DNMT3A in acute myelogenous leukemia and myelodysplastic syndrome, our results suggest that inhibition of de novo DNA methylation may be a common oncogenic mechanism in leukemogenesis..[Alexey:2012]
- These results suggest that Dal B02 may be an effective carrier for the radioimmunotherapy of human B-cell CLL and other appropriate B-cell lymphomas, especially in the progressive phase of B-cell CLL, which is usually not amenable to currently available therapeutic modalities..[Zhu:1994]{Human}
- Occurrence of 13q14 deletions between D13S273 and D13S25 in B-cell chronic lymphocytic leukemia (B-CLL) suggests that the region contains a tumor suppressor gene..[van:2003]{Human}
- Results obtained suggest that the relationships between examined soluble form of TNF family proteins may influence the development of B-cell chronic lymphocytic leukemia..[Ewa:2005]{Human}
- These results further support the concept of distinct CLL subgroups based on karyotype. Furthermore, the association of trisomy 12 and complex abnormalities with mixed-cell morphology may have implications for clonal evolution in CLL..[Kroft:1997]{Human}
- We used comparative genomic hybridization (CGH) to explore the cytogenetic relationship between typical and atypical B-cell CLL. Results showed a similar pattern of chromosome gains and losses detected in typical and atypical B-cell CLL, suggesting they are related disorders..[O'Connor:2000]{Human}
- These findings suggest that the development of PRCA in B-cell CLL may result from suppression of CFU-E proliferation by T gamma cells..[Mangan:1983]{Human}
- A probable adverse prognosis is suggested for this group of patients, likely related to clonal evolution..[Christian:2003]{Human}
- Results from patients in stages with equal prognosis (Rai I and II, Rai III and IV) were similar and when these results were grouped the observed differences were highly significant and clearly correlated with all prognostic groups..[Hautekeete:1987]{Human}
|
[Survival Time]:0.2810828
- Eight previously treated and four untreated patients with B cell chronic lymphocytic leukemia ( CLL) received 20 X 10(6) U/m2 recombinant leukocyte interferon clone A (rIFN-alpha A) intramuscularly three times a week for 8 weeks..[Schulof:1985]{Human}
- The prognostic effect of 11q deletion on survival strongly depended on the age: in patients less than 55 years old, the median survival time was significantly shorter in the deletion group (64 months v 209 months; P < .001), whereas in patients > or = 55 years old there was no significant difference (94 months v 111 months; P = .82). 11q deletions identify a new clinical subset of B-CLL characterized by extensive lymph node involvement. In younger B-CLL patients, this aberration is an important predictor of survival..[D?hner:1997]{Human}
- Rai and Binet staging classifications and TTM score system retained their prognostic value in this CLL population. In addition, cases fulfilling criteria of "smoldering" CLL, had a very long survival (75% survival probability at 16 years)..[Molica:1994]{Human}
- However, in a subgroup of CLL patients with good prognoses or early-stage disease (Rai stages 0-II, Binet stages A,B; beta2-M </= 2.8 mg/dL), lower levels of VEGF were associated with shorter survival times..[Aguayo:2000]{Human}
- CLL cells were cleared from blood in 95% patients in a median time of 21 days. CR or nodular PR in the bone marrow was achieved in 66% of the patients and most patients achieved this after 18 weeks of treatment. An 87% OR (29% CR) was achieved in the lymph nodes..[Jeanette:2002]{Human}
- Short telomere length and high telomerase activity were significantly associated with a shorter median survival (P=0.02 and P <0.001), and telomerase activity was the most significant prognostic factor for overall survival in B-CLL (P <0.001)..[Bechter:1998]{Human}
- Administration of 50 micrograms/mouse of Dal B02, an IgG1 (kappa) MAb directed against surface-associated antigens of human B-cell CLL, significantly prolonged the survival of D10-1-inoculated nude and SCID mice..[Zhu:1994]{Human}
- Tumor necrosis factor (TNF) superfamily, involving membrane receptors and ligands are important for the growth and survival of leukemic B cells..[Ewa:2005]{Human}
|
[Clinical Presentation]:0.27983385
- Soluble CD23 (sCD23) and beta-2 microglobulin (beta2-m) are reliable prognostic parameters in B-cell chronic lymphocytic leukemia ( CLL); however, their merit over well-established clinical variables such as clinical stages, bone marrow (BM) histology and lymphocyte doubling time (LDT) remains to be defined..[Molica:1999]{Human}
- Seventy-six consecutive untreated patients with B cell chronic lymphocytic leukemia (B-CLL) and classified according to Binet's staging system were studied at the clinical presentation. Several immunologic parameters (number of total and T circulating lymphocytes and their surface membrane immunoglobulin [Smlg] phenotypes and levels of serum Ig) were evaluated with the aim of identifying a biologic marker of prognostic relevance..[Baldini:1985]{Human}
- These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease..[Rosenwald:2001]{Human}
- A large number of prognostic factors are available to help predict the outcome of patients who present with B-cell chronic lymphocytic leukemia (B-CLL). These include clinical stage, leukemic cell morphology, lymphocyte doubling time, the pattern of infiltration in bone marrow trephine biopsies, cytogenetic abnormalities, p53 function and serum factors such as beta-2 microglobulin..[Tryfonia:2004]{Human}
- The patient presented a complex immunologic deficiency, revealed not only by the monoclonality of the B lymphocytes and their low degree of maturity, but also by the almost total absence of T helper lymphocytes, by the high reduction in NK activity, by the very scarce proliferative response to the polyclonal mitogens PHA, ConA and PWM, and by a complete anergy to the skin test of delayed reactivity..[Contu:1986]{Human}
- On the basis of the present experiments, it is suggested that the defective colony growth of T-cell fractions in B-cell CLL may be related to the low number of OKT4-positive cells plated, which are known to be mainly responsible for the colony generation in agar culture..[Neri:1982]{Human}
- In conclusion, bright expression of CD20 or sIg light chain is not an unusual feature in B-CLL and may not influence clinical presentation or short-term prognosis..[Tefferi:1996]{Human}
- Deoxynucleoside kinases are key enzymes in deoxyribonucleoside salvage, activating several clinically important chemotherapeutic drugs..[Eriksson:1994]{Human}
- Increased numbers of T lymphocytes were present in marrow aspirates of these patients..[Mangan:1983]{Human}
- All patients experienced acute and chronic graft-versus-host disease and responded clinically to SCT..[Mattsson:2000]{Human}
|
[CLL Development]:0.27004075
- These genes may be important in the development of nitrogen mustard (NM) drug resistance in B-cell chronic lymphocytic leukemia (B-CLL). Using Western blot analysis, we examined the levels of Bcl-2, Bax, Bcl-X and p53 protein expression and determined whether the levels of these proteins correlated with in vitro drug resistance in CLL patients' lymphocyte samples. Our investigations suggest that in CLL, NM drug resistance develops without any detectable alteration of Bcl-2, Bax or Bcl-X..[Christodoulopoulos:1998]{Human}
- After i.v. or i.p. inoculation of 5 x 10(6) D10-1 cells, a subclone of an Epstein-Barr virus transformed human B-cell chronic lymphocytic leukemia ( CLL) line, 100% of nude mice developed solid or ascites tumors and died within 17-60 days of tumor inoculation..[Zhu:1994]{Human}
- A 70-year-old woman with a 2-year history of B-cell chronic lymphocytic leukemia ( CLL) developed headache, fever, chills, and weakness..[Lee:1995]{Human}
- Richter syndrome (RS) is well known as a secondary high-grade lymphoma, mostly diffuse large B-cell lymphoma (DLBCL) developed in patients with B-cell chronic lymphocytic leukemia (B-CLL)..[Naoya:2003]{Human}
- In order to identify regulatory genes involved in the development of an apoptosis-resistant phenotype in patients with chemotherapy refractory B-cell chronic lymphocytic leukemia (B-CLL) expression of apoptosis-regulating genes in B-CLL cells was quantified using cDNA arrays and RT-PCR..[Alejo:2004]{Human}
- Results obtained suggest that the relationships between examined soluble form of TNF family proteins may influence the development of B-cell chronic lymphocytic leukemia..[Ewa:2005]{Human}
- In vitro studies were performed in two patients with B-cell chronic lymphocytic leukemia who developed pure red cell aplasia (CLL-PRCA)..[Mangan:1983]{Human}
- These findings suggest that the development of PRCA in B-cell CLL may result from suppression of CFU-E proliferation by T gamma cells..[Mangan:1983]{Human}
- Although 3% to 5% of patients with B-cell CLL may develop higher-grade lymphoma, usually the lymphoma is of B-cell lineage and often represents a histologic manifestation of clonal evolution..[Lee:1995]{Human}
|
[Patients with Acute]:0.26484126
- We determined the expression levels of the mdr1 and mdr3 multidrug-resistance genes (also known as PGY1 and PGY3, respectively) in peripheral blood cells from 69 adult patients with acute and chronic leukemias, using an RNase protection assay. Expression of mdr1 was found in samples from patients with acute nonlymphocytic leukemia (13 of 17), chronic myelocytic leukemia (CML, chronic phase, 10 of 10; blast crisis, three of four), acute lymphocytic leukemia (ALL, eight of 11), B-cell chronic lymphocytic leukemia (B-CLL, 17 of 17), hairy cell leukemia (HCL, one of two), and T-cell prolymphocytic leukemia (one of one), but not in B-cell prolymphocytic leukemia (B-PLL, 0 of seven). Expression of mdr3 was only detected in samples from B-cell lymphocytic leukemias: CML, lymphoid blast crisis (one of one), B-cell ALL (two of two), B-CLL (17 of 17), B-PLL (seven of seven), and HCL (two of two). In vitro drug uptake studies by on-line flow cytometry showed that in leukemia cells expressing either mdr1 or mdr3, the steady-state accumulation of daunorubicin could be significantly increased by addition of cyclosporine and, to a lesser extent, by verapamil. Because cyclosporine and verapamil are known as inhibitors of the mdr1-encoded P-glycoprotein drug-efflux pump, and because the mdr1 and mdr3 genes are highly homologous, our data suggest that the mdr3 gene encodes a functional drug pump in B-cell lymphocytic leukemias. The results of this study may have implications for clinical therapy for acute or chronic leukemias expressing the mdr1 or mdr3 gene, in particular, treatment with combinations of cytotoxic drugs plus agents that reverse multidrug resistance. Since mdr1 and mdr3 are frequently expressed in untreated as well as treated leukemia, such combination therapy should be considered for untreated patients as well as treated patients..[Herweijer:1990]{Human}
- It has been reported that telomeres are shortened in acute leukemias where the cell turnover is high. B-cell chronic lymphocytic leukemia ( CLL) is a particularly interesting haematological malignancy in regard to telomere dynamics because most of the malignant cells in CLL are mitotically inactive. In this study, we analysed the telomere length in patients with B-cell CLL in a comparison with the control group by using ddPRINS technique..[Sukru:2006]{Human}
- Strong evidence exists for an association between high vascular endothelial growth factor (VEGF) levels and poor prognoses in patients with solid tumors and acute leukemia. Using Western blot analysis and solid-phase radioimmunoassay, we measured cellular VEGF levels in B-cell chronic lymphocytic leukemia ( CLL) samples from 225 patients and correlated these levels with disease characteristics and prognoses. The median VEGF level in CLL samples was 7.26 times the median level detected in normal peripheral blood mononuclear cells..[Aguayo:2000]{Human}
- The coexistence of acute myeloid leukemia and chronic lymphocytic leukemia in the same patient is rare. The majority of the cases correspond to patients that developed acute leukemia during the evolutionary course of a chronic lymphatic leukemia following treatment with chemotherapy drugs. We report a case of acute myelomonocytic leukemia concurrent with untreated B-cell chronic lymphocytic leukemia in which the use of flow cytometry analysis with a large panel of monoclonal antibodies, allowed the demonstration of different pathological populations and determine immunophenotyping patterns. Published cases of simultaneous chronic lymphocytic leukemia and acute leukemia are reviewed..[Viviana:2010]{Human}
- In both cases of acute leukemia, the mutation was restricted to one allele and could not be detected in remission samples. Those data suggest that activation of members of the ras oncogene family, typified by K-ras, may be less important in disease pathogenesis in leukemias such as B-CLL that arise from a more committed progenitor..[Browett:1988]{Human}
- By using a combination oligonucleotide probe hybridization and restriction enzyme polymorphism analysis, a series of 48 cases of B-cell chronic lymphocytic leukemia were investigated for activating point mutations at codons 12, 13 and 61 of the K-ras proto-oncogene. A small series of acute leukemias (seven with acute lymphoblastic leukemia (ALL), 11 with acute myeloid leukemia (AML)) were examined in parallel..[Browett:1988]{Human}
- Similarly, CLL samples with high Tcl1 expression showed a decrease in DNA methylation compared with CLL samples with low Tcl1 expression. Given the previous reports of inactivating mutations of DNMT3A in acute myelogenous leukemia and myelodysplastic syndrome, our results suggest that inhibition of de novo DNA methylation may be a common oncogenic mechanism in leukemogenesis..[Alexey:2012]
- At the HLA typing, the patient was DR5, as are most classical KS and/or B-CLL patients..[Contu:1986]{Human}
- All patients experienced acute and chronic graft-versus-host disease and responded clinically to SCT..[Mattsson:2000]{Human}
|
[Monoclonal Antibodies]:0.251817
- The coexistence of acute myeloid leukemia and chronic lymphocytic leukemia in the same patient is rare. The majority of the cases correspond to patients that developed acute leukemia during the evolutionary course of a chronic lymphatic leukemia following treatment with chemotherapy drugs. We report a case of acute myelomonocytic leukemia concurrent with untreated B-cell chronic lymphocytic leukemia in which the use of flow cytometry analysis with a large panel of monoclonal antibodies, allowed the demonstration of different pathological populations and determine immunophenotyping patterns. Published cases of simultaneous chronic lymphocytic leukemia and acute leukemia are reviewed..[Viviana:2010]{Human}
- B cell chronic lymphocytic leukemia ( CLL) is a disease of expanding monoclonal B cells whose B cell receptor (BCR) mutational status defines 2 subgroups; patients with mutated BCRs have a more favorable prognosis than those with unmutated BCRs. CLL B cells express a restricted BCR repertoire including antibodies with quasi-identical complementarity-determining region 3 (CDR3), which suggests specific antigen recognition. The antigens recognized by CLL antibodies may include autoantigens since about half of CLL B cells produce autoreactive antibodies. However, the distribution of autoreactive antibodies between Ig heavy-chain variable-unmutated (IgV-unmutated) CLL (UM-CLL) and IgV-mutated CLL (M-CLL) is unknown. To determine the role of antibody reactivity and the impact of somatic hypermutation (SHM) on CLL antibody specificity, we cloned and expressed in vitro recombinant antibodies from M- and UM-CLL B cells and tested their reactivity by ELISA. We found that UM-CLL B cells expressed highly polyreactive antibodies whereas most M-CLL B cells did not. When mutated nonautoreactive CLL antibody sequences were reverted in vitro to their germline counterparts, they encoded polyreactive and autoreactive antibodies. We concluded that both UM-CLLs and M-CLLs originate from self-reactive B cell precursors and that SHM plays an important role in the development of the disease by altering original BCR autoreactivity..[Maxime:2005]{Human}
- In order to obtain more information on the pattern of CD11c-positivity in otherwise typical B-cell chronic lymphocytic leukemia ( CLL), we analyzed immunological and clinico-pathological features of 99 such patients studied with two different monoclonal antibodies (MoAbs)..[Molica:1995]{Human}
- Blood mononuclear cells from 540 newly diagnosed, unselected patients with B-cell chronic lymphocytic leukemia ( CLL) were examined by immunofluorescence flow cytometry for a panel of surface membrane markers, including IgM and IgD, the monoclonal antibodies anti-CD3, -5, -20, -21, -22, -FMC7, and, for the final 125 patients, anti-CD23..[Geisler:1991]{Human}
- This phase II study determined the efficacy and safety of alemtuzumab, a humanized anti-CD52 monoclonal antibody, delivered subcutaneously as first-line therapy, over a prolonged treatment period of 18 weeks in 41 patients with symptomatic B-cell chronic lymphocytic leukemia (B-CLL)..[Jeanette:2002]{Human}
- The patient presented a complex immunologic deficiency, revealed not only by the monoclonality of the B lymphocytes and their low degree of maturity, but also by the almost total absence of T helper lymphocytes, by the high reduction in NK activity, by the very scarce proliferative response to the polyclonal mitogens PHA, ConA and PWM, and by a complete anergy to the skin test of delayed reactivity..[Contu:1986]{Human}
- Among the promising prognostic markers is flowcytometric analysis of CD38 on the monoclonal B cells in CLL..[Boonstra:2005]{Human}
- Addition of CD38 to the flow cytometry antibody panel for B-CLL analysis is a relatively easy way to obtain important prognostic information..[Boonstra:2005]{Human}
|
[Western Countries]:0.21800888
- B-cell chronic lymphocytic leukemia ( CLL) is a highly common form of leukemia characterized by the accumulation of long-lived, functionally inactive, mature appearing neoplastic B lymphocytes. In addition, immune disturbances such as hypogammaglobulinemia and autoimmune phenomena (particularly, autoimmune hemolytic anemia) are frequently found in CLL patients [1-2]. The etiology of CLL is unknown. In contrast with other leukemias, there is no relationship between CLL and exposure to radiation or other cytotoxic agents. A genetic basis is highly likely since there are differences in the incidence of CLL in different countries (e.g., CLL accounts for 30%-40% of all the leukemias in Western countries as compared to 5%-10% in Asian countries) and the risk of contracting CLL is higher among persons with first-degree relatives with the disease [3]. Because the incidence of CLL increases with age and the longer life expectancy of the general population, the age of patients at diagnosis is increasing..[Montserrat:1997]{Human}
- B-cell chronic lymphocytic leukemia (B-CLL) is the most common B-cell leukemia among older populations in Western countries..[Avadhut:2007]{Human}
- B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in Western countries and results from the accumulation of B-lymphocytes which are functionally abnormal and predominantly non-cycling in vivo. Consequently, it is important to understand why B-CLL cells accumulate in GO phase. Since TGF-beta is an important negative regulator of the immune system, a loss of responsiveness to this factor might provide a selective advantage to B-CLL cells..[Lagneaux:1998]{Human}
- B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in Westerners..[Kunihiro:2005]{Human}
- B-cell chronic lymphocytic leukemia (B-CLL), a clonal expansion of B CD5+ cells, is the most frequent type of adult leukemia in western countries..[Monika:2004]{Human}
|
[Telomere Length]:0.20853376
- It has been reported that telomeres are shortened in acute leukemias where the cell turnover is high. B-cell chronic lymphocytic leukemia ( CLL) is a particularly interesting haematological malignancy in regard to telomere dynamics because most of the malignant cells in CLL are mitotically inactive. In this study, we analysed the telomere length in patients with B-cell CLL in a comparison with the control group by using ddPRINS technique..[Sukru:2006]{Human}
- The use of telomere length and telomerase expression as new biological markers in cancer patients requires their correlation with disease prognosis. We, therefore, correlated the mean telomere length based on a telomere restriction fragment assay and the activity of telomerase measured with a telomeric repeat amplification protocol with clinical data and overall survival in 58 patients with B cell chronic lymphocytic leukemia (B-CLL)..[Bechter:1998]{Human}
- Short telomere length and high telomerase activity were significantly associated with a shorter median survival (P=0.02 and P <0.001), and telomerase activity was the most significant prognostic factor for overall survival in B-CLL (P <0.001)..[Bechter:1998]{Human}
- We hypothesise that the telomeric erosion in CLL may reflect the dominance of malignant cells with an abnormally long life span..[Sukru:2006]{Human}
- Our findings imply that shortened telomeres in CLL may be reflecting the "history" of the disease and serve as an independent prognostic factor..[Sukru:2006]{Human}
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[Associated with Poor Prognosis]:0.20386046
- Strong evidence exists for an association between high vascular endothelial growth factor (VEGF) levels and poor prognoses in patients with solid tumors and acute leukemia. Using Western blot analysis and solid-phase radioimmunoassay, we measured cellular VEGF levels in B-cell chronic lymphocytic leukemia ( CLL) samples from 225 patients and correlated these levels with disease characteristics and prognoses. The median VEGF level in CLL samples was 7.26 times the median level detected in normal peripheral blood mononuclear cells..[Aguayo:2000]{Human}
- A role for ATM in the development of sporadic T-cell chronic leukemias is supported by the finding of loss of heterozygosity at 11q22-23 and ATM mutations in leukemias carrying TCL-1 rearrangements. Approximately 14% of B-cell chronic lymphocytic leukemia (B-CLL), the most common adult leukemia, carry deletions of the long arm of chromosome 11 at 11q22-23. Loss of heterozygosity at 11q22-23 and, more recently, absence of ATM protein, have been associated with poor prognosis in B-CLL..[Bullrich:1999]{Human}
- Trisomy of chromosome 12 is one of the commonest cytogenetic abnormalities in the karyotype in chronic lymphocytic leukemia ( CLL). It is associated with atypical morphology of lymphocytes, progressing disease and poor survival. A high incidence abnormality in the B-cell CLL is deletion of chromosome 13 (13q14) detected by using modern diagnostic methods such as southern blot hybridization and fluorescence in situ hybridization. It occurs in 51% of the CLL patients and in as much as 70% in mantle-cell lymphoma..[Karnolsky:2001]{Human}
- The usage of the immunoglobulin (Ig) V(H)3-21 gene is associated with poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) despite V(H) gene mutation status..[Susann:2005]{Human}
- T-lymphocyte colony formation in agar culture was investigated in 20 untreated B-cell Chronic Lymphocytic Leukemia ( CLL) patients in stage O. As compared to the controls, colony growth was very poor when unseparated peripheral-blood lymphocytes from CLL-patients were seeded. The number of colonies was greatly higher when T-cell enriched fractions from CLL were plated; however, they failed to reach the normal range even in this experimental condition..[Neri:1982]{Human}
- In this study we analyse these gene families by quantitative real-time PCR to investigate whether expression levels and the B-cell chronic lymphocytic leukemia (B-CLL) phenotype are associated..[Harikrishnan:2005]{Human}
- In conclusion, CGH abnormality was associated with poor prognosis in Japanese B-CLL, and features of Japanese B-CLL, compared to chromosomal abnormalities of Western B-CLL in the literature, include a lower incidence of any abnormality in particular regarding gain of 12q, with the exception of a higher incidence of gains at 3q..[Kunihiro:2005]{Human}
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[Investigated]:0.18214357
- Therapeutic options are limited and the prognosis is poor for patients with fludarabine-refractory B-cell chronic lymphocytic leukemia ( CLL). Bortezomib induces apoptosis in vitro in CLL cells, both alone and in combination, including in cells resistant to fludarabine or other agents. The aim of the current randomized, open-label, Phase II study was to investigate the clinical activity of bortezomib in patients with fludarabine-refractory B-cell CLL..[Stefan:2006]{Human}
- We propose that lymph node stromal cells play an important role in the differentiation of B cells through direct contact and that HN cells will be useful for investigating the differentiation pathway of chronic B cell leukemia cells..[Takeuchi:1995]{Human}
- T-lymphocyte colony formation in agar culture was investigated in 20 untreated B-cell Chronic Lymphocytic Leukemia ( CLL) patients in stage O. As compared to the controls, colony growth was very poor when unseparated peripheral-blood lymphocytes from CLL-patients were seeded. The number of colonies was greatly higher when T-cell enriched fractions from CLL were plated; however, they failed to reach the normal range even in this experimental condition..[Neri:1982]{Human}
- ZAP-70 and CD38 expression can identify B-cell chronic lymphocytic leukemia with an inferior clinical outcome. Many groups have investigated the meaning of the expression of these two proteins and the correlation with the bad prognosis in B-CLL..[Nicolas:2007]{Human}
- In this study we analyse these gene families by quantitative real-time PCR to investigate whether expression levels and the B-cell chronic lymphocytic leukemia (B-CLL) phenotype are associated..[Harikrishnan:2005]{Human}
- We investigated 38 cases of B-cell chronic lymphocytic leukemia (B-CLL) for the presence of non-productive rearrangements in the S(mu) regions and defined for the first time the molecular nature of these rearrangements..[Elena:2002]{Human}
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[Conclude]:0.1804524
- We conclude that the hypoproliferative anemia occurring in the course of B cell CLL is due to gradual accumulation in the marrow of T gamma lymphocytes which suppress erythroid progenitor cell growth..[Mangan:1985]{Human}
- We conclude that IS ODN including CpG ODN can induce apoptosis of most B-CLL samples..[Bernd:2005]{Human}
- We conclude that RFP2, c13ORF1, and a chromosome 13-specific ST13-like gene, FAM10A4, are the most likely candidates for such a type of B-CLL TSG..[van:2003]{Human}
- We conclude that deletions in 6q21 occur in 7% of B-CLL and identify a subgroup of patients characterized by a larger tumor mass but no inferior outcome..[Stilgenbauer:1999]{Human}
- We conclude that bfl-1 may be an important regulator of B-CLL apoptosis, which could contribute to disease progression and resistance to chemotherapy, and as such represent a future potential therapeutic target..[Alejo:2004]{Human}
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[Stimulation Cells]:0.17984772
- The chromosome constitutions of stimulated lymphocytes in 21 untreated cases with B-cell chronic lymphocytic leukemia (B-CLL) were examined..[Sadamori:1984]{Human}
- To clarify the cell cycle duration of stimulated cells in B cell chronic lymphocytic leukemia (B-CLL), sister chromatid differentiation (SCD) methodology was utilized..[Sadamori:1984]{Human}
- We have evaluated genomic aberrations by conventional cytogenetics and fluorescence in situ hybridization (FISH) analysis in a series of 57 Argentinean B-cell chronic lymphocytic leukemia (B-CLL) patients. The studies were performed on stimulated peripheral blood lymphocytes..[Christian:2003]{Human}
- We examined the most optimal method to transform B-CLL cells into efficient antigen-presenting cells (APC) using activating cytokines, by triggering toll-like receptors (TLRs) using microbial pathogens and by CD40 stimulation with CD40L-transfected fibroblasts..[Hoogendoorn:2004]{Human}
- In contrast to primary B-CLL cells as stimulator cells, these malignant APCs were capable of inducing the generation of B-CLL-reactive CD8(+) CTL lines and clones from HLA class I-matched donors..[Hoogendoorn:2004]{Human}
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[Typical and Atypical B-cell CLL]:0.16400474
- Peripheral blood lymphocyte morphology and karyotype were correlated across the spectrum of cytogenetic abnormalities in 78 previously karyotyped cases of B-cell chronic lymphocytic leukemia ( CLL). Cases were classified according to French-American-British morphologic criteria as typical CLL or CLL, mixed-cell type; the latter category was divided into CLL with a mixture of small and large cells and CLL with increased prolymphocytes ( CLL/PL)..[Kroft:1997]{Human}
- B-cell chronic lymphocytic leukemia ( CLL) can be classified as typical or atypical based on morphologic and immunophenotypic features..[O'Connor:2000]{Human}
- In order to obtain more information on the pattern of CD11c-positivity in otherwise typical B-cell chronic lymphocytic leukemia ( CLL), we analyzed immunological and clinico-pathological features of 99 such patients studied with two different monoclonal antibodies (MoAbs)..[Molica:1995]{Human}
- We used comparative genomic hybridization (CGH) to explore the cytogenetic relationship between typical and atypical B-cell CLL. Results showed a similar pattern of chromosome gains and losses detected in typical and atypical B-cell CLL, suggesting they are related disorders..[O'Connor:2000]{Human}
- We previously have shown the strong association between trisomy 12 as detected by FISH and CD11a expression in atypical B-cell CLL..[O'Connor:2000]{Human}
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[Adhesion Molecules]:0.14902902
- The classification of CD5-negative/CD10-negative chronic B-cell leukemias (CD5-/CD10- CBL) can be problematic. Most of these cases may represent leukemic non-Hodgkin's lymphoma (NHL) other than B-cell chronic lymphocytic leukemia (BCLL); nonetheless, some investigators still advocate the term "CD5-negative BCLL." Because adhesion molecule (AdMol) expression patterns reflect the biology of lymphoid neoplasms, we studied a series of 106 B-cell lymphoproliferative disorders, including CD5+ BCLL (n = 56), NHL other than BCLL (n = 35), and CD5-/CD10- CBL (excluding hairy cell leukemia and prolymphocytic leukemia) with no prior history of NHL (n = 15) for expression of components of the very late antigen-4 complex (alpha4/beta1 integrin (CD49d/CD29)), components of the mucosal addressin-cell adhesion molecule receptor (alpha4(CD49d)/beta7 integrin), and L-selectin (CD62L)..[Finn:2001]{Human}
- One of the main reasons for interest in these molecules is that they may play a determining role in neoplastic transformation and diffusion; in particular, in lymphoproliferative syndromes, a lack of cell adhesiveness or an abnormal adhesion pattern in neoplastic lymphocytes may free these cells from regulation, thus contributing towards the development of leukemia and/or lymphoma. Studies of VLA expression in B-cell leukemia/lymphomas show a modulation of VLA3 and VLA4 reactivity. The most interesting element is the identification of a VLA3/VLA4 pattern associated with B-cell chronic lymphocytic leukemia (B-CLL) characterised by a reduced expression of VLA4 and the constant expression of VLA3..[Baldini:1994]{Human}
- Most of these genes code either for cell adhesion molecules (L-selectin, integrin-beta2) or for factors inducing cell adhesion molecules (IL-1beta, IL-8, EGR1), suggesting that prognosis of this disease may be related to a defect in lymphocyte trafficking..[Stratowa:2001]{Human}
- Spontaneous apoptosis of B-CLL cells in vitro was significantly lower in samples with good prognosis cytogenetics when compared to samples with poor prognosis cytogenetics. In contrast, B-CLL cells from samples with good prognosis cytogenetics exhibited higher basal expression of molecules involved in costimulation, cellular adhesion, and antigen presentation, and induced significantly more T-cell proliferation in mixed lymphocyte cultures..[Jahrsd?rfer:2005]{Human}
- There was no correlation between the expression of the adhesion molecules and clinical and laboratory parameters except for CD18 which was expressed on a significantly (P < 0.05) higher number of leukemic cells in CLL with more advanced stages. This study demonstrates that even closely related B cell leukemia/lymphomas have a certain well defined and strictly variable adhesion profile which is characteristic of the disease entity and therefore, the adhesion profile may offer additional information useful for differential diagnosis and study of disease pathogenesis..[Csanaky:1997]{Human}
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[CpG ODN]:0.13367534
- We previously demonstrated that treatment of B cell chronic lymphocytic leukemia (B-CLL) cells with one class of IS ODN, CpG ODN, alters their phenotype and increases their immunogenicity..[Bernd:2005]{Human}
- It is important that these changes are seen not only with CpG ODN but with ODN that lack the classical CpG motif..[Bernd:2005]{Human}
- We conclude that IS ODN including CpG ODN can induce apoptosis of most B-CLL samples..[Bernd:2005]{Human}
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[(Other)]:1.001358E-5
- We investigated the effects of stromal cells, obtained from lymph nodes with various lymphoid disorders and characterized immunocytochemically as fibroblasts, on the maturation of a cell line "HN" established from an atypical PLL (prolymphocytic leukemia) having phenotypic characteristics of both CLL ( chronic lymphocytic leukemia) and HCL (hairy cell leukemia). Coculture with stromal cells, irrespective of the kind of lymphoid disease affecting the lymph node, induced a plasmacytoid cytology in HN cells, an increase of cIg gamma, and decreases of sIg gamma, CD5, CD21, HC2, and B-ly7..[Takeuchi:1995]{Human}
- Deletions or translocations of 13q, most commonly involving band 13q14, belong to the most frequent structural chromosome abnormalities in B-cell chronic lymphocytic leukemia (B-CLL). In a combined metaphase and interphase cytogenetic study using conventional G-banding analysis and fluorescence in situ hybridization (ISH) we previously analysed the retinoblastoma susceptibility gene (RB-1) and its chromosomal locus 13q14 in 35 patients with chronic B-cell leukemias. We report here on the interphase cytogenetic analysis of 109 cases with chronic B-cell leukemias [B-CLL = 90; B-prolymphocytic leukemia (B-PLL) = 6, hairy cell leukemia (HCL) = 13]; a subset of 49 patients (B-CLL = 45; B-PLL = 4) was studied by conventional G-banding analysis..[D?hner:1995]{Human}
- The original observation that sera from patients with chronic B-cell lymphocytic leukemia (B-CLL) contain high amounts of soluble CD23 (sCD23), which reflect disease activity and tumor load has been confirmed by numerous reports and serial determinations of sCD23 are now recognized as important indicators of disease progression..[Schwarzmeier:2004]{Human}
- Leukemia cell survival also could be enhanced by exogenous IFN-gamma or anti-CD40 presented on Fc gamma RII (CDw32)-expressing L cells, but not by exogenous IL-4, IL-6, or monomeric human IgG. We find that Ag acts directly on the leukemia B cells to inhibit apoptosis. This effect could be mimicked by cross-linking the leukemia cells' surface IgM receptors with immobilized murine mAb specific for human Ig mu-chains, but not by immobilized mAb of irrelevant specificity. In contrast to most follicular NHL, this leukemia B cell population does not have evidence of bcl-2 gene rearrangement. Also, in contrast to non-Hodgkin's lymphomas and most B cell CLL, these cells do not express detectable amounts of bcl-2. Finally, although capable of inhibiting apoptosis, surface Ig receptor cross-linking does not induce expression of bcl-2 in these variant leukemia cells. We hypothesize that the lack of bcl-2 expression may render these leukemia cells particularly dependent upon the survival signal(s) derived from surface Ig receptor cross-linking. This state may represent an early stage in leukemia/lymphomagenesis, possibly accounting for the intraclonal diversity observed in the Ig V genes expressed by certain CD5- B cell leukemias and lymphomas..[Kobayashi:1994]{Human}
- Most B-cell chronic lymphocytic leukemias and a small normal subset of B lymphocytes express the T-cell-associated CD5 antigen; expression of other T-cell antigens has been reported only rarely. The authors report two cases of typical B-cell chronic lymphocytic leukemia, seen during 1 year, in which two-color flow cytometric analysis documented expression of the T-cell-associated CD8 antigen by the monoclonal B cells..[Koelliker:1994]{Human}
- We studied a variant CD5- B cell chronic lymphocytic leukemia ( CLL) cell population that produces pathologic IgM kappa rheumatoid factor autoantibodies. In contrast to common CD5+ B cell CLL, this variant leukemia cell population displays intraclonal diversity in its expressed Ig V genes, similar to that noted for follicular B cell non-Hodgkin's lymphomas. Also, in contrast to common B cell CLL, these leukemia cells rapidly undergo cell death hours after being placed in tissue culture..[Kobayashi:1994]{Human}
- One leiomyosarcoma and one extra-skeletal osteosarcoma showed a dCK levels comparable to those found in normal lymphocytes (84 +/- 6 and 109 +/- 4 ng/mg), while other sarcoma samples contained levels comparable to the gastrointestinal adenocarcinomas (20 +/- 7 ng/mg, n = 12). We confirm that dCK is expressed constitutively and predominantly in lymphoid cells, but conclude that a significant expression may be found in non-lymphoid tissues as well, with increased levels in the corresponding tumor tissue. 2-Chlorodeoxyadenosine (CdA), an antileukemic agent used in treatment of hairy cell leukemia and chronic lymphocytic leukemias (B-CLL), is phosphorylated by dCK which was used as the selective substrate for this enzyme..[Eriksson:1994]{Human}
- The goal of this study was to evaluate the relation of chromosomal abnormalities detected by fluorescence in situ hybridization (FISH) in the prognosis of B-cell chronic lymphocytic leukemia (B-CLL) patients..[Beyhan:2008]{Human}
- To establish xenograft models of human B-cell chronic lymphocytic leukemia ( CLL), we inoculated 5 x 10(6) D10-1 cells, a subline of Epstein-Barr virus (EBV)-transformed human B-cell CLL with a marker chromosomal anomaly, into SCID or irradiated nude mice by the intravenous (i.v.) or intraperitoneal (i.p.) route..[Zhu:1994]{Human}
- Soluble CD23 (sCD23) was proposed as a marker of disease activity and as an important prognostic parameter in B-cell chronic lymphocytic leukemia (B-CLL)..[Saka:2006]{Human}
- The surface phenotype of these cells was identical to that of circulating lymphocytes, indicating meningeal involvement of leukemia, a rare complication in B-CLL. At the time of this WBC elevation, 24% of circulating lymphocytes had prominent nucleoli, indicating progression of the disease to CLL/prolymphocytic leukemia..[Naoko:2005]{Human}
- The genetic features of B-cell chronic lymphocytic leukemia ( CLL) are currently being reassessed by molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH). Conventional cytogenetic studies by chromosome banding are difficult in CLL mainly because of the low in vitro mitotic activity of the tumor cells, which leads to poor quantity and quality of metaphase spreads. Molecular genetic analyses are limited because candidate genes are known for only a few chromosomal aberrations that are observed in CLL. FISH was found to be a powerful tool for the genetic analysis of CLL as it overcomes both the low mitotic activity of the CLL cells and the lack of suitable candidate genes for analysis..[Stilgenbauer:2001]{Human}
- CD5+, CD23+) B-cell chronic lymphocytic leukemia ( CLL). Although changes of CD20 antigen density did not correlate with clinical parameters representative of either tumor mass (i.e. clinical stage, histological pattern of bone marrow involvement, absolute peripheral blood lymphocytosis) or disease progression (i.e. lymphocyte doubling time), a trend toward a better life-expectancy was observed in the low CD20 expression group compared with the high CD20 expression group (p = 0.05; relative risk of death, 0.51, 95% confidence interval, 0.24-1.04)..[Molica:1998]{Human}
- We performed a feasibility study systematically comparing large-scale gene expression profiles with clinical features in human B-cell chronic lymphocytic leukemia (B-CLL). cDNA microarrays were employed to determine the expression levels of 1,024 selected genes in 54 peripheral blood lymphocyte samples obtained from patients with B-CLL..[Stratowa:2001]{Human}
- High levels of dCK were found in normal mononuclear leukocytes (91-145 ng dCK/mg protein) and in B-cell chronic lymphocytic leukemia (80 +/- 30 ng/mg, n = 23). Hairy cell leukemia contained lower levels (28 +/- 23 ng/mg, n = 7), as did unexpectedly three samples of T-cell chronic lymphocytic leukemia (18 +/- 14 ng/mg). Phytohemaglutinine stimulation of normal lymphocytes did not lead to any substantial increase in either dCK activity or expression (less than 2.5-fold)..[Eriksson:1994]{Human}
- In this report, we have examined the expression and distribution of HsRad51 protein in lymphocytes from patients with B-CLL to see whether the expression of HsRad51 is associated with NM damage to the malignant B lymphocytes, specifically chlorambucil (CLB), which is the standard alkylating agent used to treat patients with B-CLL. We have analyzed the intracellular distribution of HsRad51 protein in these lymphocytes before and after treatment with CLB by immunofluorescence. In vitro CLB treatment induces Rad51 expression, as measured by increased immunopositive staining in all CLL samples. In the CLB-resistant CLL lymphocytes, there was a linear correlation between induction of Rad51 protein at 5.4 microM CLB and the in vitro LD50 dose of CLB. Surprisingly, although it has been reported that Rad51 is induced in S phase and only 10% of cells from cell lines expressed positive immunostaining for Rad51, our CLL lymphocytes, which were not subjected to in vitro drug exposure, were 90% positive for Rad51, despite their nonproliferative state, which suggests that there is chronic activation of the protein. Our results suggest that CLB activates HsRad51-directed recombination repair and that this process may be important in NM drug-induced cytotoxicity..[Christodoulopoulos:1999]{Human}
- All the tumor-inoculated mice had histologically confirmed metastases in lymph nodes, and most of them also had metastases in one or more internal organs..[Zhu:1994]{Human}
- B cell chronic lymphocytic leukemia (B-CLL) is a common clonal B cell leukemia that is often accompanied by a multitude of immune abnormalities..[Bartik:1998]{Human}
- Our data suggests that FISH analysis of B-CLL patients provides important diagnostic, clinical, and prognostic information which may help clinicians assess the prognosis and make appropriate treatment decisions..[Beyhan:2008]{Human}
- Moreover, we propose that the lack of chromosomal translocations in B-CLL may be related to their derivation from marginal zone B cells, since somatic hypermutation and Ig class switch, the processes that generate chromosome translocations in most germinal center (GC)-derived malignancies, are no longer active in marginal zone B cells. Also, we discuss similarities and differences between B-CLL and hairy cell leukemia (HCL) and suggest that also HCL may be derived from a post-GC memory or marginal zone B cell..[Klein:2005]{Human}
- B cell chronic lymphocytic leukemia ( CLL) is a malignancy of the CD5+ B cells..[Rassenti:1993]{Human}
- A 70-year-old woman was diagnosed with B-cell-type chronic lymphocytic leukemia (B-CLL) in May 2001. Initial white blood cell (WBC) count was 37 x 10(9)/l and most of the cells were mature small lymphocytes..[Naoko:2005]{Human}
- On analyzing the survival curves of our patients according to different Smlg phenotypes, we found that patients with only mu-type Smlg had a poorer prognosis (P less than .05) than those with mu-type plus delta-type; this difference was even more significant (P less than .01) in patients in stage A, whereas there were no statistical differences in those in stages B and C. Because the appearance of surface heavy chain of delta-type could be an expression of cell maturation, these results suggest that in B-CLL the presence of phenotypically more mature leukemic cells may correlate with better clinical prognosis, particularly in the early phase of the disease..[Baldini:1985]{Human}
- B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous malignant disease, both in terms of molecular abnormalities and clinical course. The most frequent chromosomal aberrations in B-CLL are deletions on 13q, 11q, and 17p, and trisomy 12, all of which are of prognostic significance..[Urban:2004]{Human}
- In parallel, the accurate evaluation of the incidence of chromosome aberrations in CLL by FISH allows the correlation of genetic abnormalities with clinical disease manifestations and outcome. In particular, 17p abnormalities and deletions in 11q22-q23 have already been shown to be among the most important independent prognostic factors identifying subgroups of patients with rapid disease progression and short survival..[Stilgenbauer:2001]{Human}
- Allogeneic stem cell transplantation following reduced-intensity conditioning is being evaluated in patients with advanced B-cell chronic lymphocytic leukemia (B-CLL)..[Hoogendoorn:2004]{Human}
- Several authors have studied the T-lymphocyte subpopulations in B-cell chronic lymphocytic leukemia (B-CLL), but previous studies were performed after preceding enrichment procedures, which are known to cause selective losses of certain subpopulations..[Hautekeete:1987]{Human}
- The true frequency of the CD8-positive B-cell chronic lymphocytic leukemia, any clinical implications, and the possibility of a normal subset of CD5-positive CD8-positive B cells remain to be determined..[Koelliker:1994]{Human}
- On the other hand, most cases without abnormal clones had not received treatment for relatively long periods before and after cytogenetic examination. These findings may indicate that cytogenetic results can be utilized as a parameter for treatment and prognosis in B-CLL..[Sadamori:1984]{Human}
- Our data indicate that good prognosis cytogenetics correlates with less spontaneous apoptosis but greater in vitro immunogenicity. These findings could have significant implications on the design of future therapeutic approaches in patients with CLL, and the likelihood of response based on cytogenetics..[Jahrsd?rfer:2005]{Human}
- Serum sCD23 is increased in B-CLL patients and can be used in the clinical follow-up of the disease in prediction of the tumor mass and prognosis..[Saka:2006]{Human}
- They have become the most commonly used markers to trace loss of heterozygosity in tumors..[Urban:2004]{Human}
- In the past two decades, significant progress has been made in CLL [4-10]. This review summarizes recent advances in the biology, diagnosis, and therapy of CLL..[Montserrat:1997]{Human}
- These findings suggest that p53 mutations are relatively rare in B-cell CLL, and largely predominate or may even be restricted to patients with 17p monosomy (who constitute about 5% of all B-cell CLL patients in large published series)..[Fenaux:1992]{Human}
- High levels of tumor necrosis factor-alpha (TNF-alpha) and soluble interleukin-2 receptor (sIL-2R) indicated advanced disease, and patients with increased levels pre- and post-SCT were also those with the most long-lasting PCR-detectable MRD post-SCT..[Mattsson:2000]{Human}
- Furthermore, we observed a positive correlation between HMTaseI expression levels and stage of leukemia suggesting that changes in the methylation patterns in B-CLL may represent deregulation of the epigenetic repertoire that also include the methylation dependent binding proteins, MBD2 and MeCP2..[Harikrishnan:2005]{Human}
- One of the most perplexing questions regarding epigenetic modifications and leukemogenesis is the relationship with DNA methyltransferases (DNMT's)..[Harikrishnan:2005]{Human}
- Finally, on the basis combined increased serum levels of beta2-m and sCD23, a better stratification of low- and intermediate-risk patients could be obtained, thus allowing the formulation of a clinico-biological staging for CLL..[Molica:1999]{Human}
- Although no objective responses were achieved in patients with fludarabine-refractory B-cell CLL, single-agent bortezomib demonstrated biologic activity..[Stefan:2006]{Human}
- Seventy-eight percent of the B-CLL patients with lymphocyte doubling time (LDT) <12 months and 24% of patients with LDT >12 months had high sCD23 levels (P = 0.008)..[Saka:2006]{Human}
- CD20 intensity was classified as weak in 62% of patients, moderate in 12%, and strong in 26%..[Tefferi:1996]{Human}
- By applying different algorithms, the data enabled an efficient class discrimination of the V(H)3-21+ subset based on 27 or 57 genes..[Susann:2005]{Human}
- This requires more precise research, as new anti-leukemic drugs influence the regulation of apoptosis of neoplastic B lymphocytes..[Monika:2004]{Human}
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