scholarly journals Regulatory B lymphocyte functions should be considered in chronic lymphocytic leukemia

2016 ◽  
Vol 5 (5) ◽  
pp. e1132977 ◽  
Author(s):  
Audrey Mohr ◽  
Yves Renaudineau ◽  
Cristina Bagacean ◽  
Jacques-Olivier Pers ◽  
Christophe Jamin ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Lymphocyte ◽  
Lymphocytic Leukemia

scholarly journals B lymphocyte subpopulations in chronic lymphocytic leukemia

Blood ◽  
1976 ◽  
Vol 47 (2) ◽  
pp. 229-235
Author(s):  
RA Rudders
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Lymphocyte ◽  
Lymphocyte Subpopulations ◽  
Lymphocytic Leukemia ◽  
Clinicopathologic Characteristics ◽  
Homogeneous Population ◽  
Clear Cut ◽  
Igg Synthesis ◽  
A Minor ◽  
Ig Synthesis

We have defined two subpopulations of B lymphocytes in chronic lymphocytic leukemia (CLL). The major variant (termed typical) was characterized by the presence of a relatively homogeneous population of small-to-medium-sized lymphocytes with low-density SmIgM and no evidence of intracellular Ig synthesis. A minor group (termed atypical) was identified by the presence of a pleomorphic cell population with few small lymphocytes. The predominant SmIg was IgG, which was detected intracellularly as well as in the serum. The atypical group appeared to be an arrest at a later stage of differentiation where a switch from IgM to IgG synthesis and secretion had occurred. Clinical correlation suggested several clear-cut differences in clinicopathologic characteristics, but the median survivals for both groups at 2 yr was nearly identical.

Aberrant expression of B-lymphocyte stimulator by B chronic lymphocytic leukemia cells: a mechanism for survival

Blood ◽  
2002 ◽  
Vol 100 (8) ◽  
pp. 2973-2979 ◽  
Author(s):  
Anne J. Novak ◽  
Richard J. Bram ◽  
Neil E. Kay ◽  
Diane F. Jelinek
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocyte ◽  
Leukemic Cell ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Aberrant Expression ◽  
B Lymphocyte Stimulator

B-cell chronic lymphocytic leukemia (B-CLL) is defined by the accumulation of CD5+ B cells in the periphery and bone marrow. This disease is not characterized by highly proliferative cells but rather by the presence of leukemic cells with significant resistance to apoptosis and, therefore, prolonged survival. B-lymphocyte stimulator (BLyS) is a newly identified tumor necrosis factor (TNF) family member shown to be critical for maintenance of normal B-cell development and homeostasis and it shares significant homology with another TNF superfamily member, APRIL. The striking effects of BLyS on normal B-cell maintenance and survival raises the possibility that it may be involved in pathogenesis and maintenance of hematologic malignancies, including B-CLL. In this study, we investigated the status of APRIL and BLyS expression, as well as their receptors, in this disease. All B-CLL patient cells studied expressed one or more of 3 known receptors for BLyS; however, the pattern of expression was variable. In addition, we demonstrate for the first time that B-CLL cells from a subset of patients aberrantly express BLyS and APRIL mRNA, whereas these molecules were not detectable in normal B cells. Furthermore, we provide in vitro evidence that BLyS protects B-CLL cells from apoptosis and enhances cell survival. Because these molecules are key regulators of B-cell homeostasis and tumor progression, leukemic cell autocrine expression of BLyS and APRIL may be playing an important role in the pathogenesis of this disease.

scholarly journals B lymphocyte subpopulations in chronic lymphocytic leukemia

Blood ◽  
1976 ◽  
Vol 47 (2) ◽  
pp. 229-235 ◽  
Author(s):  
RA Rudders
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Lymphocyte ◽  
Lymphocyte Subpopulations ◽  
Lymphocytic Leukemia ◽  
Clinicopathologic Characteristics ◽  
Homogeneous Population ◽  
Clear Cut ◽  
Igg Synthesis ◽  
A Minor ◽  
Ig Synthesis

Abstract We have defined two subpopulations of B lymphocytes in chronic lymphocytic leukemia (CLL). The major variant (termed typical) was characterized by the presence of a relatively homogeneous population of small-to-medium-sized lymphocytes with low-density SmIgM and no evidence of intracellular Ig synthesis. A minor group (termed atypical) was identified by the presence of a pleomorphic cell population with few small lymphocytes. The predominant SmIg was IgG, which was detected intracellularly as well as in the serum. The atypical group appeared to be an arrest at a later stage of differentiation where a switch from IgM to IgG synthesis and secretion had occurred. Clinical correlation suggested several clear-cut differences in clinicopathologic characteristics, but the median survivals for both groups at 2 yr was nearly identical.

scholarly journals Chronic Lymphocytic Leukemia B Cells Can Undergo Somatic Hypermutation and Intraclonal Immunoglobulin VHDJH Gene Diversification

2002 ◽  
Vol 196 (5) ◽  
pp. 629-639 ◽  
Author(s):  
Carmela Gurrieri ◽  
Peter McGuire ◽  
Hong Zan ◽  
Xiao-Jie Yan ◽  
Andrea Cerutti ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Lymphocyte ◽  
Somatic Hypermutation ◽  
Point Mutations ◽  
Single Strand Conformation Polymorphism ◽  
Lymphocytic Leukemia ◽  
Gene Diversification

Chronic lymphocytic leukemia (CLL) arises from the clonal expansion of a CD5+ B lymphocyte that is thought not to undergo intraclonal diversification. Using VHDJH cDNA single strand conformation polymorphism analyses, we detected intraclonal mobility variants in 11 of 18 CLL cases. cDNA sequence analyses indicated that these variants represented unique point-mutations (1–35/patient). In nine cases, these mutations were unique to individual submembers of the CLL clone, although in two cases they occurred in a large percentage of the clonal submembers and genealogical trees could be identified. The diversification process responsible for these changes led to single nucleotide changes that favored transitions over transversions, but did not target A nucleotides and did not have the replacement/silent nucleotide change characteristics of antigen-selected B cells. Intraclonal diversification did not correlate with the original mutational load of an individual CLL case in that diversification was as frequent in CLL cells with little or no somatic mutations as in those with considerable mutations. Finally, CLL B cells that did not exhibit intraclonal diversification in vivo could be induced to mutate their VHDJH genes in vitro after stimulation. These data indicate that a somatic mutation mechanism remains functional in CLL cells and could play a role in the evolution of the clone.

Deregulation of Aiolos expression in chronic lymphocytic leukemia is associated with epigenetic modifications

Blood ◽  
2011 ◽  
Vol 117 (6) ◽  
pp. 1917-1927 ◽  
Author(s):  
Katy Billot ◽  
Jérémie Soeur ◽  
Fanny Chereau ◽  
Issam Arrouss ◽  
Hélène Merle-Béral ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Survival ◽  
B Lymphocyte ◽  
Histone H3 ◽  
Nuclear Factor Κb ◽  
Epigenetic Modifications ◽  
Lymphocytic Leukemia ◽  
Nuclear Factor ◽  
Gain Access

Abstract Chronic lymphocytic leukemia (CLL) is characterized by a clonal accumulation of mature neoplastic B cells that are resistant to apoptosis. Aiolos, a member of the Ikaros family of zinc-finger transcription factors, plays an important role in the control of mature B lymphocyte differentiation and maturation. In this study, we showed that Aiolos expression is up-regulated in B-CLL cells. This overexpression does not implicate isoform imbalance or disturb Aiolos subcellular localization. The chromatin status at the Aiolos promoter in CLL is defined by the demethylation of DNA and an enrichment of euchromatin associated histone markers, such as the dimethylation of the lysine 4 on histone H3. These epigenetic modifications should allow its upstream effectors, such as nuclear factor-κB, constitutively activated in CLL, to gain access to promoter, resulting up-regulation of Aiolos. To determine the consequences of Aiolos deregulation in CLL, we analyzed the effects of Aiolos overexpression or down-regulation on apoptosis. Aiolos is involved in cell survival by regulating the expression of some Bcl-2 family members. Our results strongly suggest that Aiolos deregulation by epigenetic modifications may be a hallmark of CLL.

Effects of Rituximab on JAK-STAT and NF-κB signaling pathways in acute lymphoblastic leukemia and chronic lymphocytic leukemia

2019 ◽  
Vol 44 (4) ◽  
pp. 499-509 ◽  
Author(s):  
Ayşegül Dalmızrak ◽  
Nur Selvi Günel ◽  
Burçin Tezcanlı Kaymaz ◽  
Fahri Şahin ◽  
Güray Saydam ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Signaling Pathways ◽  
Cell Lines ◽  
B Lymphocyte ◽  
Lymphoblastic Leukemia ◽  
Lymphocytic Leukemia ◽  
Protein Expressions ◽  
Apoptotic Effect

AbstractObjectivesRituximab is a monoclonal antibody that targets the B-lymphocyte surface antigen CD20. It is used in the treatment of some diseases including B-cell chronic lymphocytic leukemia (B-CLL). There are a lot of data regarding effect of Rituximab on lymphoma cells. But, there is no satisfactory information about the effect of Rituximab on the signaling pathways in leukemia cells. In this study, it was aimed to understand the effect of Rituximab on JAK-STAT and NF-κB signaling pathways in B-cell acute lymphoblastic leukemia (B-ALL) and B-CLL.Material and methodsApoptotic effect of Rituximab in the TANOUE (B-ALL) and EHEB (B-CLL) cell lines were evaluated by using the Annexin V method. mRNA expression levels of STAT3 and RelA were analysed by quantitative RT-PCR (Q-PCR). Alterations in STAT3 and RelA protein expressions were detected by using a chromogenic alkaline phosphatase assay after Western Blotting.ResultsRituximab had no apoptotic effect on both cell lines. Complement-mediated cytotoxicity was only detected in EHEB cells. mRNA and protein expressions of STAT3 and RelA genes were decreased following Rituximab treatment.ConclusionOur preliminary results suggest that the use of Rituximab might be effective in B-ALL though both signaling pathways.

Early prediction of outcome and response to alemtuzumab therapy in chronic lymphocytic leukemia

Blood ◽  
2004 ◽  
Vol 103 (6) ◽  
pp. 2027-2031 ◽  
Author(s):  
Andy C. Rawstron ◽  
Ben Kennedy ◽  
Paul Moreton ◽  
Anita J. Dickinson ◽  
Matthew J. Cullen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocyte ◽  
Lymphocytic Leukemia ◽  
Early Prediction ◽  
Close Monitoring ◽  
Patients At Risk ◽  
Invasive Method ◽  
Improve Patient Management

Abstract Alemtuzumab therapy is effective for some refractory chronic lymphocytic leukemia (CLL), but identifying responders requires at least 8 weeks of therapy. Early identification of nonresponders would minimize toxicity and/or facilitate more effective strategies. The aim of this study was to identify a minimally invasive method for early prediction of response and relapse. Flow cytometric monitoring was performed in 887 blood samples and 201 marrow samples from 43 patients undergoing intravenous alemtuzumab therapy. Although the absolute lymphocytosis was resolved in all patients by week 4, significant depletion of bone marrow tumor only occurred if circulating B-lymphocyte counts were persistently less than 0.001 × 109/L, which was rare in nonresponders. The majority of patients (16/28) who did not benefit from a full course of therapy were identified with 100% positive predictive value using the following algorithm: peripheral B-cell count greater than 0.001 × 109/L at week 2 with less than 1 log depletion of circulating B cells between weeks 2 and 4. Monitoring CLL levels after treatment identified patients at risk of early disease progression and could potentially improve patient management. During alemtuzumab therapy, bone marrow CLL depletion only occurs after abrogation of circulating tumor, requiring close monitoring of circulating B-cell levels. If validated in prospective studies, blood monitoring at 2 and 4 weeks may be used to optimize therapy.

scholarly journals Frequency of monoclonal B-cell lymphocytosis in relatives of patients with chronic lymphocytic leukemia

2016 ◽  
pp. 81-86
Author(s):  
Rossana Villegas Gracia ◽  
Catalina Franco Alzate ◽  
Javier Rendón Henao ◽  
José Domingo Torres Hernández ◽  
Patricia Elena Jaramillo Arbelaez
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocytes ◽  
B Lymphocyte ◽  
Chronic Lymphocytic Leukemia Patient ◽  
Lymphocytic Leukemia ◽  
Total Leukocyte Count ◽  
Female Participant ◽  
Color Flow ◽  
The One

Introduction: Monoclonal B-cell lymphocytosis is a symptom free condition characterized by the circulation of small clonal population of B lymphocytes in peripheral blood (less than 5x109/L) expressing an immunophenotype similar to chronic lymphocytic leukemia. Different studies based on big hospital series have manifested a higher risk in subjects with monoclonal B-cell lymphocytosis to progress to a chronic lymphocytic leukemia. The behavior of this hematologic entity is unknown therefore its frequency in sporadic chronic lymphocytic leukemia patient relatives was determined. Methods: Transversal descriptive study, 8 color flow cytometry was performed using two of the tubes of the Euro Flow recommended panel, with modifications, for the diagnose of chronic lymphoproliferative disorders of B lymphocytes; besides, a fluorescence in situ hybridization was performed. univariate and bivariate analyses of the information were performed. Results: Monoclonal B-cell lymphocytosis frequency found in 51 analyzed relatives was 2%, it was a female participant, 59 years old, with a total leukocyte count of 7.7x109/L and a B lymphocyte count of 0.124x109/L; from these, 0.04x109/L were clonal cells with restrictions of the kappa light chain. Rearrangements of the IGH gene (14q32) were found. Conclusion: Monoclonal B-cell lymphocytosis was detected in one relative of a patient with sporadic chronic lymphocytic leukemia in a frequency similar to the one reported in general population.

scholarly journals Dual B and T markers in acute and chronic lymphocytic leukemia

Blood ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 16-20
Author(s):  
KA Foon ◽  
RJ Billing ◽  
PI Terasaki
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocyte ◽  
Surface Membrane ◽  
Lymphocytic Leukemia ◽  
Rosette Formation ◽  
Leukemic Cells ◽  
Cell Markers ◽  
Membrane Immunoglobulin

Leukemic cells from 20 patients with chronic lymphocytic leukemia (CLL) and 60 patients with acute lymphocytic leukemia (ALL) were studied for T- and B-lymphocyte cell surface membrane markers. B-cell markers included surface membrane immunoglobulin, erythrocyte-antibody complement rosette formation, and B-cell (a-like or HLA-DR) antigens detected by a B-cell antiserum. T-cell markers included spontaneous sheep red blood cell rosette formation and a cytotoxic reaction to a specific T-cell antiserum. Seven patients with CLL and two with ALL had dual B and T markers. We propose that dual B- and T-cell markers are more common in CLL and ALL patients than previously reported. With newer and more sensitive tests for identification of B and T cells, this observation may be recognized more frequently.

Sign in / Sign up

Export Citation Format

Share Document