scholarly journals Profiles of Surface Mosaics on Chronic Lymphocytic Leukemias Distinguish Stable and Progressive Subtypes

2013 ◽  
Vol 16 (2) ◽  
pp. 231 ◽  
Author(s):  
Pauline Yu-Hsiu Huang ◽  
Philippa Kohnke ◽  
Larissa Belov ◽  
Giles Best ◽  
Stephen Peter Mulligan ◽  
...  
Keyword(s):  
Lymphocytic Leukemia ◽  
Research Groups ◽  
Considerable Effort ◽  
Antibody Microarray ◽  
Aberrant Expression ◽  
Surface Mosaics ◽  
Patients At Risk ◽  
Extensive Surface ◽  
Surface Profiles ◽  
Disease Signature

Purpose. Chronic lymphocytic leukemia (CLL) is a heterogeneous disease, some patients may survive for many years, while 20-30% of patients progress and may die within several years. Currently, there is not a single procedure that enables accurate prognosis and triaging of those patients who need immediate and aggressive treatment. All CLL cells are characterised by the expression of the B-cell antigens CD19, CD20, CD21, CD22 and CD23, with aberrant expression of the T-cell antigen CD5. Methods. We have developed a CD antibody microarray (DotScan) containing 182 immobilised CD antibodies that has been used to obtain extensive surface profiles of CLL cells obtained from 96 patients. Results. Of these 182 antigens, 27 were significantly differentially expressed between stable, stable-progressive and progressive CLL. Some of these antigens are not expressed on normal B-cells and may be targets for therapeutic antibodies against CLL. Unsupervised hierarchical clustering of the surface profiles from 96 patients showed that those with progressive CLL could be distinguished based solely upon this ‘disease signature’. The sensitivity (proportion of actual positives correctly identified) was 67.9%, the specificity (proportion of negatives correctly identified) was 77.5%, and the accuracy was 71.9%. Conclusions. Considerable effort by a number of research groups has resulted in identification of individual markers for progressive CLL, but their collective use is yet to provide a test that identifies CLL patients at risk. Data presented here provide a basis for development of a simple test using an antibody microarray. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Aberrant Expression of TLR2, TLR7, TLR9, Splicing Variants of TLR4 and MYD88 in Chronic Lymphocytic Leukemia Patients

2021 ◽  
Vol 10 (4) ◽  
pp. 867
Author(s):  
Katarzyna Skorka ◽  
Paulina Wlasiuk ◽  
Agnieszka Karczmarczyk ◽  
Krzysztof Giannopoulos
Keyword(s):  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
Cytotoxic T Cells ◽  
Lymphocytic Leukemia ◽  
Aberrant Expression ◽  
Downstream Signaling ◽  
Splicing Variants ◽  
High Level ◽  
Time To First Treatment ◽  
First Time

Functional toll-like receptors (TLRs) could modulate anti-tumor effects by activating inflammatory cytokines and the cytotoxic T-cells response. However, excessive TLR expression could promote tumor progression, since TLR-induced inflammation might stimulate cancer cells expansion into the microenvironment. Myd88 is involved in activation NF-κB through TLRs downstream signaling, hence in the current study we provided, for the first time, a complex characterization of expression of TLR2, TLR4, TLR7, TLR9, and MYD88 as well as their splicing forms in two distinct compartments of the microenvironment of chronic lymphocytic leukemia (CLL): peripheral blood and bone marrow. We found correlations between MYD88 and TLRs expressions in both compartments, indicating their relevant cooperation in CLL. The MYD88 expression was higher in CLL patients compared to healthy volunteers (HVs) (0.1780 vs. 0.128, p < 0.0001). The TLRs expression was aberrant in CLL compared to HVs. Analysis of survival curves revealed a shorter time to first treatment in the group of patients with low level of TLR4(3) expression compared to high level of TLR4(3) expression in bone marrow (13 months vs. 48 months, p = 0.0207). We suggest that TLRs expression is differentially regulated in CLL but is similarly shared between two distinct compartments of the microenvironment.

scholarly journals MicroRNAs as Haematopoiesis Regulators

2013 ◽  
Vol 2013 ◽  
pp. 1-20 ◽  
Author(s):  
Ram Babu Undi ◽  
Ravinder Kandi ◽  
Ravi Kumar Gutti
Keyword(s):  
Blood Cells ◽  
Erythroid Differentiation ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Aberrant Expression ◽  
Hematopoietic Stem ◽  
Complex Process ◽  
Development And Differentiation ◽  
Multiple Myelomas

The production of different types of blood cells including their formation, development, and differentiation is collectively known as haematopoiesis. Blood cells are divided into three lineages erythriod (erythrocytes), lymphoid (B and T cells), and myeloid (granulocytes, megakaryocytes, and macrophages). Haematopoiesis is a complex process regulated by several mechanisms including microRNAs (miRNAs). miRNAs are small RNAs which regulate the expression of a number of genes involved in commitment and differentiation of hematopoietic stem cells. Evidence shows that miRNAs play an important role in haematopoiesis; for example, myeloid and erythroid differentiation is blocked by the overexpression of miR-15a. miR-221, miR-222, and miR-24 inhibit the erythropoiesis, whereas miR-150 plays a role in B and T cell differentiation. miR-146 and miR-10a are downregulated in megakaryopoiesis. Aberrant expression of miRNAs was observed in hematological malignancies including chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myelomas, and B cell lymphomas. In this review we have focused on discussing the role of miRNA in haematopoiesis.

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.

Intensive intravenous methotrexate and mercaptopurine treatment of higher-risk non-T, non-B acute lymphocytic leukemia: A Pediatric Oncology Group study.

1994 ◽  
Vol 12 (7) ◽  
pp. 1383-1389 ◽  
Author(s):  
B Camitta ◽  
D Mahoney ◽  
B Leventhal ◽  
S J Lauer ◽  
J J Shuster ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Lymphocytic Leukemia ◽  
Remission Induction ◽  
Intrathecal Therapy ◽  
Free Survival ◽  
Continuation Therapy ◽  
Potential Efficacy ◽  
Patients At Risk ◽  
B Lineage

PURPOSE To determine the potential efficacy and toxicity of intravenous (i.v.) methotrexate (MTX) and mercaptopurine (MP) as postremission intensification treatment for children with B-lineage acute lymphoblastic leukemia (ALL) at higher risk to relapse. PATIENTS AND METHODS Eighty-three patients (age 1 to 20 years) with higher-risk B-lineage ALL were entered onto this protocol. Following standard four-drug remission induction, 80 patients received 12 intensive 2-week cycles of MTX/MP: MTX 200 mg/m2 i.v. push, then 800 mg/m2 i.v. 24-hour infusion on day 1; MP 200 mg/m2 i.v. in 20 minutes, then 800 mg/m2 i.v. 8-hour infusion day 2; MTX 20 mg/m2 intramuscularly day 8; and MP 50 mg/m2 by mouth days 8 to 14. Age-based triple intrathecal therapy (MTX, hydrocortisone, and cytarabine) was administered for CNS prophylaxis. Continuation therapy was weekly MTX/MP (as on days 8 to 14) for 2 years. RESULTS Eighty-one patients (98%) entered remission. There were 28 relapses (marrow, n = 11; marrow and CNS, n = 2; isolated CNS, n = 9; testes, n = 5; ovaries, n = 1). No overt relapse occurred during the intensive phase of therapy. The event-free survival (EFS) rate at 4 years is 57.4% +/- 9.1% (SE). Hematologic, mucosal, and infectious toxicities were seen in 12%, 9%, and 5% of intensive MTX/MP courses, but were generally mild. CONCLUSION Combined data from this and our previous trial suggest that intensive MTX/MP may produce long-term disease-free survival in 70 to 75% of children with B-lineage ALL. In comparison to other intensive regimens, intensive MTX/MP is easy to administer, effective, and relatively nontoxic. If patients at risk for failure of MTX/MP can be identified prospectively, more aggressive regimens could be restricted to this smaller (25% to 30%) cohort.

Surface profiles for subclassification of chronic lymphocytic leukemia

2012 ◽  
Vol 53 (6) ◽  
pp. 1046-1056 ◽  
Author(s):  
Pauline Y. Huang ◽  
O. Giles Best ◽  
Larissa Belov ◽  
Stephen P. Mulligan ◽  
Richard I. Christopherson
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Surface Profiles

Aberrant Expression of Trail in B Chronic Lymphocytic Leukemia (B-CLL) Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4976-4976
Author(s):  
Mario Tiribelli ◽  
Elisa Barbarotto ◽  
Claudio Celeghini ◽  
Angela Michelutti ◽  
Giorgio Zauli ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Lymphocytes ◽  
Lymphocytic Leukemia ◽  
Aberrant Expression ◽  
High Affinity ◽  
Viable Cells ◽  
Biological Potential ◽  
Group 3 ◽  
Recombinant Trail ◽  
Group 1

Abstract Chronic lymphocytic leukemia (CLL) is a quintessential example of human malignancies that are caused primarily by defect in apoptosis. Defects in apoptotic pathways contribute also to chemoresistance and can promote resistance to cellular immune responses. TNF-related apoptosis inducing ligand (TRAIL), interacts with four high affinity membrane receptors (TRAIL-R1 – R4): R1 and R2 are thought to transducer apoptotic signals, while R3 and R4 may act as “decoy” receptors, protecting cells from apoptosis. Despite its potential anti–cancer activity, TRAIL alone has a low cytotoxic activity on B-CLL, and no data are available on the expression of TRAIL and its biological potential function in B-CLL. We examined the expression of TRAIL in peripheral blood CD19+/CD5+ B lymphocytes from 44 patients affected by CLL at diagnosis, the susceptibility of B-CLL cells to recombinant TRAIL and the role of endogenous membrane-bound TRAIL on autologous cell survival. Each B-CLL patient had a follow up time of 12 to 24 months from diagnosis and was clinically stable. None of the patients received chemotherapy. Lymphocytes from normal PBMC revealed an absent or dim expression of TRAIL. Surface TRAIL was detected in all 44 B-CLL examined, at variable intensity from patient to patient, but with an overall significantly greater MFI with respect to normal lymphocytes. Higher levels of TRAIL mRNA and protein were documented in purified CLL CD19+ B lymphocytes, confirming that TRAIL was overexpressed at the transcriptional level. The addition in culture of a TRAIL-R1-Fc chimera, which binds at high affinity to surface TRAIL, significantly decreased the percentage of viable cells with respect to untreated cultures. No effects were noted when TRAIL-R1-Fc chimera was added to normal CD19+ B cells. Preincubation of TRAIL-R1-Fc chimera with recombinant TRAIL significantly counteracted the decrease of viability induced by TRAIL-R1-Fc chimera. These data indicate that surface TRAIL might be involved in a promoting a prosurvival activity, at least in some B-CLL samples. We then investigated the response in terms of cell viability to exogenously added recombinant TRAIL (1 μg/ml) of all 44 B-CLL samples examined in this study. On the basis of their response to recombinant TRAIL, B-CLL samples could be subdivided in 3 groups. In 11 patients (group 1), B-CLL cells showed a faster decline in the number of viable cells upon treatment with recombinant TRAIL. In 19 samples (group 2),no significant variation in terms of viable cell number in TRAIL-treated cultures was observed. In 14 patients (group 3), TRAIL-treatment results in a significantly higher numbers of viable cells compared to untreated cultures. At flow cytometry, B-CLL lymphocytes expressed at variable levels TRAIL-R1, TRAIL-R2 and TRAIL-R4, while TRAIL-R3 was never detected. TRAIL-R1 was expressed at low levels in a subset of B-CLL samples, while TRAIL-R2 was expressed in almost the totality of the B-CLL samples. TRAIL-R4 was detected in the majority of B-CLL lymphocytes, but at lower levels than in normal lymphocytes. Of note, the different apoptotic/survival response to recombinant TRAIL among the three groups of B-CLL samples described above, apparently did not depend on differences in death and/or decoy receptor patterns of expression. A progressive increase of TRAIL MFI was noticed from group 1 to group 3.

Acute Lymphocytic Leukemia and Down Syndrome

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. SCI-8-SCI-8
Author(s):  
Shai Izraeli
Keyword(s):  
Down Syndrome ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Mtor Inhibitors ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Aberrant Expression ◽  
Childhood All ◽  
Increased Risk ◽  
The Common

Abstract SCI-8 Children with Down syndrome are at a markedly increased risk for acute lymphoblastic leukemia (DS-ALL). These leukemias are exclusively of the B lymphoid precursor phenotype and occur in a similar age to “common” sporadic ALLs with the striking absence of infant ALL. Recent studies reveal that DS-ALLs are heterogeneous and differ from sporadic ALLs. Only about a fifth of DS-ALLs carry the common cytogenetic aberrations typical to childhood ALL. Genomic rearrangements leading to the expression of a cytokine receptor, CRLF2, are detected in 60% of DS-ALL in comparison with up to 10% of sporadic ALLs. CRLF2 heterodimerizes with Interleukin 7 receptor-α (IL7R) to form the receptor to thymic stromal lymphopoietin (TSLP). This receptor is usually present in macrophages, dendritic cells, and some T lymphocytes and participates in allergic and inflammatory processes. The aberrant expression of the TSLP receptor is DS-ALL (and sporadic ALL) is often associated with additional mutations that cause constitutive activation of the downstream JAK-STAT and mTOR growth signaling pathways. These are either lymphoid specific activating mutations of JAK2 or JAK1 or mutations in CRLF2 or IL7R that cause ligand-independent receptor dimerization. The role of the trisomy in selecting these somatic abnormalities is presently unknown. Clinically, the prognosis of DS-ALL is inferior to sporadic ALL mainly because of increased treatment toxicity. However, recent data suggest that the inferior outcome may also be related to the genetic properties of the leukemic cells and that excessive chemotherapy dose reduction may not be appropriate for these patients. Therefore increased vigilance for infectious complications and optimal supportive care are required during periods of intensive chemotherapy. The common activation of the TSLP signaling pathway in DS-ALLs suggests a future for targeted therapy with JAK and/or mTOR inhibitors. Importantly, research of DS-ALL has proven relevant for the general patient population with ALL, as somatic mutations in the TSLP pathway have been discovered in children and adults with sporadic ALL. A major research challenge is the elucidation of the roles of constitutional and somatic trisomy 21 in leukemogenesis. Disclosures: No relevant conflicts of interest to declare.

Prevalence of Immunophenotypes in Neoplastic Hematology At Laboratorios Fatima De Michoacan

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4829-4829
Author(s):  
Gregorio Campos-Cabrera ◽  
Salvador Campos-Cabrera ◽  
Virgina Campos-Cabrera ◽  
Maria Mora-Torres ◽  
Miguel-Angel Gomez-Guijosa ◽  
...  
Keyword(s):  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Lymphoproliferative Disorders ◽  
Lymphocytic Leukemia ◽  
Cell Leukemia ◽  
Cell Precursor ◽  
Aberrant Expression ◽  
Flow Cytometric ◽  
Monoclonal Gammapathies ◽  
Low Prevalence

Abstract Abstract 4829 Introduction: Medical indication of flow cytometric immunophenotyping includes diagnosis, classification, prognosis and disease monitoring. This is an important tool that each time is more used in hematology. Third world countries could not stay away from this technology, effort should be made to get access to it and not only make diagnosis in morphology. Objective: To determinate the prevalence of immunophenotypes in neoplastic hematology in our region (Central-West Mexico). Material and Methods: Bone marrow samples referred to Laboratorios Fatima de Michoacan for flow cytometry immunophenotyping for neoplastic hematological disease. The protocol is based on the Report on the Second Latin American Consensus Conference for Flow Cytometric Immunophenotyping of Hematological Malignancies (Cytometry Part B (Clinical Cytometry) 2005;70B:39–44), and Immunophenotyping of acute leukemia and lymphoproliferative disorders: a consensus proposal of the European LeukemiaNet Work Package 10 (Leukemia 2011;25:567–574). Results: One hundred and seventy two cases were diagnosed. Fourteen myelodisplastic syndromes were detected. Forty five acute myeloid leukemia; M0-M1 twenty two cases, 5 with aberrant expression of CD7, one with CD19 and one CD20; M2 four cases, 1 with aberrant expression of CD 2 and 1 with CD7; M3 four cases; M4 one case; M5 twelve cases, 3 aberrant expression of CD7; M6 and M7 one case each. Sixty five B cell precursor acute lymphoblastic leukemia; BI twenty three cases, 2 with aberrant expression of CD7, and 2 aberrant expression of CD13 and one with aberrant expression of CD 33; BII twenty cases, 1 aberrant expression of CD2, 1 aberrant expression of CD5, and 4 aberrant expression of CD33; BIII twenty one cases, 1 aberrant expression of CD3; BIV one case. Five T cell precursor acute lymphoblastic leukemia. Thirty four chronic lymphoproliferative disorders; eighteen B cell chronic lymphocytic leukemia, two T cell chronic lymphocytic leukemia, seven follicular lymphoma, three mantle cell lymphoma, three splenic lymphoma with villous lymphocytes and one hairy cell leukemia One adult T cell leukemia/lymphoma. One natural killer cell leukemia (CD94+, perforin +, granzyme +) Seven monoclonal gammapathies. Conclusions: It is important to create the experience with new diagnostic tools based on the regional protocols. Low prevalence of AML M2 presumably because of classic morphologic features. Low prevalence of monoclonal gammapathies because for recent incorporation to diagnosis, treatment and response criteria; it is expected that in future this prevalence will arise. This data is complemented, whenever it is possible, with chromosomal analysis to determinate the risk and treatment. Disclosures: No relevant conflicts of interest to declare.

Notch2 is involved in the overexpression of CD23 in B-cell chronic lymphocytic leukemia

Blood ◽  
2002 ◽  
Vol 99 (10) ◽  
pp. 3742-3747 ◽  
Author(s):  
Rainer Hubmann ◽  
Josef D. Schwarzmeier ◽  
Medhat Shehata ◽  
Martin Hilgarth ◽  
Markus Duechler ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Core Promoter ◽  
Lymphocytic Leukemia ◽  
Mobility Shift ◽  
Aberrant Expression ◽  
Barr Virus ◽  
Epstein Barr ◽  
Cell Chronic Lymphocytic Leukemia

Members of the Notch family encode transmembrane receptors that modulate differentiation, proliferation, and apoptotic programs of many precursor cells, including hematopoietic progenitors. Stimulation of Notch causes cleavage followed by translocation of the intracellular domain (NotchIC) to the nucleus, where it activates transcription of CBF1 responsive genes. The aim of this study was to elucidate the mechanisms leading to the overexpression of CD23, a striking feature of B-cell chronic lymphocytic leukemia (B-CLL) cells. By electrophoretic mobility shift assays, we identified a transcription factor complex (C1) that binds sequence specific to one known and 4 newly identified putative CBF1 recognition sites in the CD23a core promoter region. With the use of Epstein-Barr virus (EBV)–infected B cells as a model for CBF1 mediated CD23a expression, C1 was found to be EBV inducible. Supershift assays revealed that the nuclear form of Notch2 is a component of C1 in B-CLL cells, supporting a model in which NotchIC activates transcription by binding to CBF1 tethered to DNA. Transient transfection of REH pre–B cells with an activated form of Notch2 induced endogenous CD23a, confirming thatCD23a is a target gene of Notch2 signaling. Finally, reverse transcription-polymerase chain reaction and kinetic analysis demonstrated that the Notch2 oncogene is not only overexpressed in B-CLL cells but might also be related to the failure of apoptosis characteristic for this disease. In conclusion, these data suggest that deregulation of Notch2 signaling is involved in the aberrant expression of CD23 in B-CLL.

scholarly journals Association of Bax Expression and Bcl2/Bax Ratio with Clinical and Molecular Prognostic Markers in Chronic Lymphocytic Leukemia

2016 ◽  
Vol 35 (2) ◽  
pp. 150-157 ◽  
Author(s):  
Ksenija Vucicevic ◽  
Vladimir Jakovljevic ◽  
Natasa Colovic ◽  
Natasa Tosic ◽  
Tatjana Kostic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Lymphocytic Leukemia ◽  
Mononuclear Cells ◽  
Prognostic Markers ◽  
Statistical Significance ◽  
Genetic Alterations ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Aberrant Expression ◽  
Mutational Status

Summary Background: In chronic lymphocytic leukemia (CLL), in vivo apoptotic resistance of malignant B lymphocytes results, in part, from the intrinsic defects of their apoptotic machinery. These include genetic alterations and aberrant expression of many apoptosis regulators, among which the Bcl2 family members play a central role. Aim: The aim of this study was to investigate the association of pro-apoptotic Bax gene expression and Bcl2/Bax ratio with the clinical features of CLL patients as well as with molecular prognostic markers, namely the mutational status of rearranged immunoglobulin heavy variable (IGHV) genes and lipoprotein lipase (LPL) gene expression. Methods: We analyzed the expression of Bax mRNA and Bcl2/Bax mRNA ratio in the peripheral blood mononuclear cells of 58 unselected CLL patients and 10 healthy controls by the quantitative reverse-transcriptase polymerase chain reaction. Results: We detected significant Bax gene overexpression in CLL samples compared to non-leukemic samples (p=0.003), as well as an elevated Bcl2/Bax ratio (p=<0.001). Regarding the association with prognostic markers, the Bcl2/Bax ratio showed a negative correlation to lymphocyte doubling time (r=−0.307; p=0.0451), while high-level Bax expression was associated with LPL-positive status (p=0.035). Both the expression of Bax and Bcl2/Bax ratio were higher in patients with unmutated vs. mutated IGHV rearrangements, but this difference did not reach statistical significance. Conclusions: Our results suggest that dysregulated expression of Bcl2 and Bax, which leads to a high Bcl2/Bax ratio in leukemic cells, contributes to the pathogenesis and clinical course of CLL.

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