scholarly journals PB1883 GLYCOPROTEIN STRUCTURES OF LEUKEMIC B-LYMPHOCYTES AND CD38 EXPRESSION IN CHRONIC LYMPHOCYTIC LEUKEMIA

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 858
Author(s):  
O. Shalay ◽  
H. Lebed ◽  
V. Barilka ◽  
O. Zotova ◽  
M. Valchuk ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Lymphocytes ◽  
Lymphocytic Leukemia ◽  
Cd38 Expression

Different Expression of FcgammaRIIb in Chronic Lymphocytic Leukemia and Human Normal B Lymphocytes

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3134-3134
Author(s):  
Carol Moreno ◽  
Rajendra Damle ◽  
Sonia Jansa ◽  
Gerardo Ferrer ◽  
Pau Abrisqueta ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocytes ◽  
Surface Membrane ◽  
Memory B Cells ◽  
Lymphocytic Leukemia ◽  
Cd38 Expression ◽  
B Cell Subsets

Abstract The Fcgamma receptors (FcγRs) are a family of molecules that modulate immune responses. FcγRIIb is an inhibitory FcγR that bears immunoreceptor tyrosine-based inhibitory motifs which transduce inhibitory signals on coligation with the surface membrane Ig of the B-cell antigen receptor (BCR). The role of FcγRIIb in controlling B cell activation through inhibition of BCR signaling has been extensively studied in animal models. Nevertheless, data on FcγRIIb are scant in human normal and neoplastic B cells, this being due to the lack of a specific antibody for human FcγRIIb. Consequently, there is little information on this receptor in chronic lymphocytic leukemia (CLL). Considering the activated nature of CLL cells and the central role of the BCR in the biology of the disease, studies of FcγRs are warranted. We used a novel specific mAb directly conjugated with Alexa 488 fluorophore that solely reacts with the human FcγRIIb (MacroGenics, Inc.) to investigate the receptors expression on CLL and normal human B cells. The study population included 84 patients with CLL and 24 age- and sex-matched controls. FcγRIIb expression was assessed as the mean fluorescence intensity (MFI) of surface membrane staining. In CLL cells, FcγRIIb was measured on CD19+CD5+ cells in combination with CD38, CD49d or CD69. Normal B cells were immunostained for CD19, CD5, IgD and CD38 expression and B cell subsets: naïve (IgD+CD38−), activated (IgD+CD38+) and memory B cells (IgD−CD38−) were studied for their relative expression of FcγRIIb. FcγRIIb expression was found significantly higher in naïve B cells compared to activated and memory B cells [median MFI: 17420 (11960–21180) vs. 11.140 (7899–16970) and 11.830 (6984–17100); p<0.001]. Significant differences were also observed between CD5− and CD5+ normal B cells. In contrast, FcγRIIb expression was lower in CLL cells than in CD5+ and CD5− normal B lymphocytes [median MFI: 6901(1034–42600), 10180 (5856–14820) and 12120 (7776–16040); p<0.05)]. Interestingly, FcγRIIb expression was variable within individual CLL clones, this being higher in CD38+ and CD49d+ cells than in CD38− and CD49d− cells (p<0.05). Furthermore, the highest density of FcγRIIb was observed on those cells which coexpressed CD38 and CD49d. In contrast, no significant differences were observed between FcγRIIb and the expression of the activation antigen CD69. Although CD69 and CD38 expression was significantly higher on unmutated IGHV cases, no correlation was found between FcγRIIb levels and IGHV mutational status. Similarly, there was no correlation between FcγRIIb and other poor prognostic variables such as ZAP-70 (≥20%), CD38 (≥ 30%) or high risk cytogenetics. Nevertheless, cases with ≥ 30% CD49d+ cells had higher FcγRIIb expression than those with <30% CD49d+ cells (p=0.006). The findings presented in this study suggest a hierarchy of FcγRIIb expression in normal B-cells, CLL cells and their subpopulations: circulating normal CD5− B cells > circulating normal CD5+ B cells > circulating CD5+ CLL B cells. In addition, although FcγRIIb is present on all normal B cell subsets its expression is higher in naïve B cells. Furthermore, in CLL FcγRIIb density is greater in CD38+ and CD49d+ cells within the clone. Although CD49d and FcγRIIb on CLL clones is linked in a direct manner, there is no relationship with FcγRIIb density and IGHV mutations, ZAP-70, CD38 and unfavorable cytogenetic markers. Finally, the relationship between FcγRIIb expression on CLL cells and functional responses to BCR and other receptor-mediated signals deserve further investigation.

scholarly journals Functional heterogeneity of B-CLL lymphocytes: dissociated responsiveness to growth factors and distinct requirements for a first activation signal

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 1105-1110
Author(s):  
S Karray ◽  
H Merle-Beral ◽  
A Vazquez ◽  
JP Gerard ◽  
P Debre ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Growth Factors ◽  
Growth Factor ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocytes ◽  
Lymphocytic Leukemia ◽  
Functional Heterogeneity ◽  
B Cell Growth Factor ◽  
Directed Growth

We studied the effects of B cell directed growth factors on B lymphocytes from 11 patients with chronic lymphocytic leukemia (B-CLL). B-CLL lymphocytes were costimulated with anti-mu antibody (Ab) and with three growth factor preparations: recombinant IL2, B cell growth factor (BCGF) (20 kiloDalton (kD) BCGF) and a high molecular weight BCGF (50 kD BCGF). IL2 was the more active factor (in six of 11 patients). The effect of IL2 was dependent on a costimulation with anti-mu Ab or occurred independently of anti-mu Ab, according to the patients. This pattern of reactivity did not correlate with the presence or absence of the IL2 receptor (IL2-R) molecule on fresh B-CLL lymphocytes. Five patients responded to the 20 kD BCGF. Although four of them were also strong responders to IL2, one strongly responded to the 20 kD BCGF and did not respond to IL2. Only one patient responded to the 50 kD BCGF. When an anti-IL2-R Ab was introduced into the culture, only the responsiveness to IL2 was abolished: thus both 20 kD and 50 kD BCGFs activate B-CLL lymphocytes independently of the IL2-R. These results show that several B cell directed growth factors can act independently to support the proliferation of B-CLL lymphocytes.

scholarly journals Characterization of the phytohemagglutinin-induced proliferating lymphocyte subpopulations in chronic lymphocytic leukemia patients using a clonogenic agar technique and monoclonal antibodies

Blood ◽  
1981 ◽  
Vol 58 (5) ◽  
pp. 1053-1055 ◽  
Author(s):  
S Davis
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
Chronic Lymphocytic Leukemia ◽  
B Lymphocytes ◽  
Peripheral Blood Lymphocytes ◽  
Lymphocytic Leukemia ◽  
Helper T Cells ◽  
Suppressor T Lymphocytes ◽  
Pha Stimulation

Abstract Peripheral blood lymphocytes from normal donors and patients with chronic lymphocytic leukemia, B-cell type, were purified into T, helper T, and suppressor T lymphocytes by fluorescence-activated cell sorting using OKT3, OKT4, and OKT8 monoclonal antibodies. The maximum response of the purified subpopulations to stimulation by phytohemagglutinin (PHA) was determined by measuring the production of colonies when the stimulated cells were grown on agar. The helper T cells in normal and CLL patients were the most responsive to PHA stimulation, although the responsiveness of helper T cells to PHA was decreased in CLL. Purified CLL B cells responded minimally to PHA stimulation, but normal B lymphocytes did not. The abnormal response of CLL lymphocytes to PHA appears to be due abnormal helper T cells, and, to a smaller extent, to the ability of CLL B lymphocytes to respond.

scholarly journals Calcium-RasGRP2-Rap1 signaling mediates CD38-induced migration of chronic lymphocytic leukemia cells

2018 ◽  
Vol 2 (13) ◽  
pp. 1551-1561 ◽  
Author(s):  
Silvia Mele ◽  
Stephen Devereux ◽  
Andrea G. Pepper ◽  
Elvira Infante ◽  
Anne J. Ridley
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Cd38 Expression ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Key Points ◽  
And Migration

Key Points Basal intracellular Ca2+ levels and migration increase with higher CD38 expression in CLL cells. Rap1 and the Rap1 guanine-nucleotide exchange factor RasGRP2 are required for CLL migration and regulated by CD38 levels.

scholarly journals Lactic dehydrogenase in normal and leukemia lymphocyte subpopulations: evidence for the presence of abnormal T cells and B cells in chronic lymphocytic leukemia

Blood ◽  
1981 ◽  
Vol 57 (2) ◽  
pp. 324-327 ◽  
Author(s):  
P Rambotti ◽  
S Davis
Keyword(s):  
T Cells ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
T Lymphocytes ◽  
B Lymphocytes ◽  
Lactic Dehydrogenase ◽  
Isozyme Pattern ◽  
Lymphocyte Subpopulations ◽  
Lymphocytic Leukemia ◽  
Ldh Activity

Abstract Lactic dehydrogenase (LDH) was quantitated and the isozyme pattern studied in lymphocyte subpopulations from normal people and patients with chronic lymphocytic leukemia (CLL). Normal T lymphocytes differed from normal B lymphocytes in having greater total LDH activity (597.2 versus 252.1). Total LDH activity in CLL T cells (347.1) was lower than normal T cells., but not significantly different than normal B cells. Total LDH activity in CLL B cells (124.6) was lower then normal B cells and normal T cells. The isozyme pattern of normal T lymphocytes showed a higher activity in the LDH-1 band (26.7% versus 5.4%) but showed a lower activity in LDH-5 band (4.3% versus 16.3%) compared to normal B cells. Chronic lymphocytic leukemia T cells could be distinguished from CLL B cells by a high LDH-5 band (22.3% versus 7.6%) and from normal T cells by a high LDH-5 band (22.3% versus 4.3%) and a low LDH-1 band (7.3% versus 26.7%). CLL B cells could be distinguished from normal B cells by a low LDH-5 band (7.6% versus 16.3%). Thus, the LDH isozyme pattern distinguishes normal T lymphocytes from normal B lymphocytes, and normal T and B lymphocytes from CLL T and B lymphocytes.

scholarly journals Spurious E rosette formation in B cell chronic lymphocytic leukemia due to monoclonal anti-sheep RBC antibody

Blood ◽  
1985 ◽  
Vol 65 (2) ◽  
pp. 270-274 ◽  
Author(s):  
LE Mills ◽  
JF O'Donnell ◽  
PM Guyre ◽  
PJ LeMarbre ◽  
JD Miller ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocytes ◽  
Lymphocytic Leukemia ◽  
Rosette Formation ◽  
Surface Markers ◽  
Simultaneous Presence ◽  
Surface Immunoglobulin ◽  
Monospecific Antisera ◽  
Cell Chronic Lymphocytic Leukemia

Abstract The apparent simultaneous presence of surface markers characteristic of both B and T cells is a phenomenon being described with increasing frequency in patients with chronic lymphocytic leukemia (CLL). We describe a patient with CLL whose B lymphocytes possessed surface immunoglobulin reactive with neuraminidase-treated sheep erythrocytes (SRBCs) and produced E rosette formation. Cytofluorography using monoclonal antibodies demonstrated the B cell nature of these cells and the absence of the SRBC receptor. Further documentation that the binding of SRBCs was mediated through immunologic reaction included E rosette formation inhibition by monospecific antisera and hemagglutination of SRBCs by a paraprotein isolated from the patient's serum. Fusion of the CLL cells with a human hypoxanthine-aminopterin- thymidine-sensitive plasma cell line resulted in the production of human hybridomas that secreted the SRBC-reactive IgM antibody. An analysis of clinical histories of CLL patients whose cells exhibited this phenomenon from both immunologic and clinical perspectives is presented.

scholarly journals V H mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1410-1416 ◽  
Author(s):  
Alexander Kröber ◽  
Till Seiler ◽  
Axel Benner ◽  
Lars Bullinger ◽  
Elsbeth Brückle ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Expression Level ◽  
Chain Gene ◽  
P Value ◽  
Prognostic Impact ◽  
Survival Times ◽  
Mutation Status ◽  
Cd38 Expression ◽  
Genomic Aberrations

In chronic lymphocytic leukemia (CLL), biologic risk factors such as immunoglobulin variable heavy chain gene (VH) mutation status, CD38 expression level, and genomic aberrations have recently been identified, but the relative prognostic impact of the individual parameters is unknown. In the current study, we analyzed VH mutation status by polymerase chain reaction and sequencing (n = 300), genomic aberrations by fluorescence in situ hybridization (+3q, 6q−, +8q, 11q−, +12q, 13q−, t(14q), 17p−) (n = 300), and CD38 expression by triple-color FACS (CD5, CD19, CD38) (n = 157) in a unicentric CLL cohort. The prognostic influence of VH mutation rate and CD38 expression level was tested by maximally selected log-rank statistics. A corrected P value (Pcor) for a cutoff level allowing the best separation of 2 subgroups with different survival probabilities was identified at 97% VH homology (95% confidence interval [CI], 96%-98% homology,Pcor <.001) and at 7% CD38 expression (95% CI, 20%-71% expression, Pcor = .02). In univariate analyses, unmutated VH genes and high CD38 expression levels predicted for shorter survival times. The overall incidence of genomic aberrations was similar in theVH unmutated and VHmutated subgroups. High-risk genomic aberrations such as 17p− and 11q− occurred almost exclusively in the VHunmutated subgroup, whereas favorable aberrations such as 13q− and 13q− as single abnormalities were overrepresented in theVH mutated subgroup. In multivariate analysis, unmutated VH, 17p deletion, 11q deletion, age, WBC, and LDH were identified as independent prognostic factors, indicating a complementary role of VH mutation status and genomic aberrations to predict outcome in CLL.

Ig V Gene Mutation Status and CD38 Expression As Novel Prognostic Indicators in Chronic Lymphocytic Leukemia

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 1840-1847 ◽  
Author(s):  
Rajendra N. Damle ◽  
Tarun Wasil ◽  
Franco Fais ◽  
Fabio Ghiotto ◽  
Angelo Valetto ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Gene Mutation ◽  
Lymphocytic Leukemia ◽  
Prognostic Indicators ◽  
Risk Category ◽  
Mutation Status ◽  
Cd38 Expression ◽  
Staging Systems ◽  
V Genes ◽  
V Gene

Abstract Cellular immunophenotypic studies were performed on a cohort of randomly selected IgM+ B-chronic lymphocytic leukemia (B-CLL) cases for which Ig VH and VL gene sequences were available. The cases were categorized based on V gene mutation status and CD38 expression and analyzed for treatment history and survival. The B-CLL cases could be divided into 2 groups. Those patients with unmutated V genes displayed higher percentages of CD38+ B-CLL cells (≥30%) than those with mutated V genes that had lower percentages of CD38+ cells (<30%). Patients in both the unmutated and the ≥30% CD38+ groups responded poorly to continuous multiregimen chemotherapy (including fludarabine) and had shorter survival. In contrast, the mutated and the <30% CD38+ groups required minimal or no chemotherapy and had prolonged survival. These observations were true also for those patients who stratified to the Rai intermediate risk category. In the mutated and the <30% CD38+ groups, males and females were virtually equally distributed, whereas in the unmutated and the ≥30% CD38+ groups, a marked male predominance was found. Thus, Ig V gene mutation status and the percentages of CD38+B-CLL cells appear to be accurate predictors of clinical outcome in B-CLL patients. These parameters, especially CD38 expression that can be analyzed conveniently in most clinical laboratories, should be valuable adjuncts to the present staging systems for predicting the clinical course in individual B-CLL cases. Future evaluations of new therapeutic strategies and drugs should take into account the different natural histories of patients categorized in these manners.

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