Factors involved in CLL pathogenesis and cell survival are disrupted by differentiation of CLL B-cells into antibody-secreting cells

Ghamlouch, Hussein; Darwiche, Walaa; Hodroge, Ahmed; Ouled-Haddou, Hakim; Dupont, Sébastien; Singh, Amrathlal Rabbind; Guignant, Caroline; Trudel, Stéphanie; Royer, Bruno; Gubler, Brigitte; Marolleau, Jean‐Pierre

doi:10.18632/oncotarget.3941

Cited by 10 publications

(17 citation statements)

References 94 publications

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“…Culturing leukemic B-cells in the CD40 system in the presence of IL-10, but not IL-4 or transforming growth factor-β ( 192 ), induced CLL B-cells to switch to IgG and IgA ( 181 ). Isotype switching of CLL B-cells following differentiation into PCs has been observed in several in vitro studies, but CLL B-cells predominantly differentiated into IgM-secreting PCs ( 14 , 18 – 21 , 193 – 196 ). Cases of CLL in which the major clone expresses Ig isotypes other than IgM and IgD, for example, IgG or IgA ( 197 , 198 ) are relatively rare (5%) ( 199 ).…”

Section: What Can the Functional Features Of Cll B-cells Tell Us Aboumentioning

confidence: 92%

Chronic Lymphocytic Leukemia B-Cell Normal Cellular Counterpart: Clues From a Functional Perspective

et al. 2018

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Chronic lymphocytic leukemia (CLL) is characterized by the clonal expansion of small mature-looking CD19+ CD23+ CD5+ B-cells that accumulate in the blood, bone marrow, and lymphoid organs. To date, no consensus has been reached concerning the normal cellular counterpart of CLL B-cells and several B-cell types have been proposed. CLL B-cells have remarkable phenotypic and gene expression profile homogeneity. In recent years, the molecular and cellular biology of CLL has been enriched by seminal insights that are leading to a better understanding of the natural history of the disease. Immunophenotypic and molecular approaches (including immunoglobulin heavy-chain variable gene mutational status, transcriptional and epigenetic profiling) comparing the normal B-cell subset and CLL B-cells provide some new insights into the normal cellular counterpart. Functional characteristics (including activation requirements and propensity for plasma cell differentiation) of CLL B-cells have now been investigated for 50 years. B-cell subsets differ substantially in terms of their functional features. Analysis of shared functional characteristics may reveal similarities between normal B-cell subsets and CLL B-cells, allowing speculative assignment of a normal cellular counterpart for CLL B-cells. In this review, we summarize current data regarding peripheral B-cell differentiation and human B-cell subsets and suggest possibilities for a normal cellular counterpart based on the functional characteristics of CLL B-cells. However, a definitive normal cellular counterpart cannot be attributed on the basis of the available data. We discuss the functional characteristics required for a cell to be logically considered to be the normal counterpart of CLL B-cells.

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Section: What Can the Functional Features Of Cll B-cells Tell Us Aboumentioning

confidence: 92%

Chronic Lymphocytic Leukemia B-Cell Normal Cellular Counterpart: Clues From a Functional Perspective

et al. 2018

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“…Higher LEF1 expression was also associated with adverse prognosis in CLL patients (Erdfelder et al ., ; Wu et al ., ). LEF1 expression levels, among other CLL‐pathogenesis‐related factors including ROR1 or PI3K, were shown to decrease when the CLL cells were forced towards differentiation to plasma cells in vitro using phorbol myristate acetate or CpG oligodeoxynucleotide, in combination with a CD40 ligand and cytokines (Gutierrez et al ., ; Ghamlouch et al ., ).…”

Section: The Role Of Wnt Signalling Pathways In Cll Pathogenesismentioning

confidence: 97%

Wnt signalling pathways in chronic lymphocytic leukaemia and B‐cell lymphomas

Janovská

Bryja

2017

British J Pharmacology

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“…Rare subpopulation of CD5 + CD27 + memory B cells could give rise for CLL cells that carry mutated IGHV [11]. It was revealed earlier that expression levels of lymphoid enhancerbinding factor 1 (LEF1), receptor tyrosine kinase-like orphan receptor 1 (ROR1), fibromodulin (FMOD), T-cell leukemia/lymphoma 1 (TCL1), Ataxin (ATXN1), early B-cell factor 1 (EBF1) and p27 are significantly different in CLL cells compared to normal B-cell analogues [18]. In our study, in addition to evaluation of B-cell stage specific TFs mRNA expression, we revealed deregulation in expression of E26-transformation specific (ETS) TFs PU.1 and SPIB in CLL cells.…”

Section: Results and Disscutionmentioning

confidence: 99%

Cd150 and Cd180 Are Involved in Regulation of Transcription Factors Expression in Chronic Lymphocytic Leukemia Cells

Gordiienko¹,

Shlapatska²,

Kholodniuk³

et al. 2017

Exp. Onc.

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Background: Sequential stages of B-cell development is stringently coordinated by transcription factors (TFs) network that include B-lineage commitment TFs (Ikaros, Runx1/Cbfb, E2A, and FOXO1), B-lineage maintenance TFs (EBF1 and PAX5) and stage specific set of TFs (IRF4, IRF8, BCL6, BLIMP1). Deregulation of TFs expression and activity is often occurs in malignant B cells. The aim of this study was to evaluate TFs expression in chronic lymphocytic leukemia cells taking into consideration CD150 cell surface expression. From other side we attempted to regulate TFs expression via CD150 and CD180 cell surface receptors. Materials and Methods: Studies were performed on normal peripheral blood B-cell subpopulations and chronic lymphocytic leukemia (CLL) cells isolated from peripheral blood of 67 primary untreated patients with CLL. Evaluation of TFs expression was performed on mRNA level using qRT-PCR and on protein level by western blot analysis. Results: Median of PAX5 and EBF1 mRNA expression was higher in cell surface CD150 positive (csCD150+) compared to csCD150- CLL cases or normal CD19+ and CD19+CD5+ B-cell subsets. Differences in mRNA expression of IRF8, IRF4 and BLIMP1 between studied groups of CLL and normal B cells were not revealed. All CLL cases were characterized by downregulated expression of PU.1 and BCL6 mRNAs in comparison to normal B cells. At the same time elevated SPIB mRNA expression level was restricted to CLL cells. Protein expression of IRF4, IRF8 and BCL6 was uniformly distributed between csCD150- and csCD150+ CLL cases. PU.1 protein and CD20 that is direct PU.1 target gene positively correlated with CD150 cell surface expression on CLL cells. Ligation of CD150 and CD180 alone or in combination upregulated IRF8 and PU.1 while downregulated the IRF4 mRNA expression. Signaling via CD150 or CD180 alone elevated the level of BCL6 mRNA. Strong downregulation of IRF4 mRNA was observed after CD150, CD180 or CD150 and CD180 coligation on CLL cells. We found that in CLL cells CD150 is a negative regulator of SPIB while CD180 is involved in upregulation of EBF1 expression level. Moreover, CD180 ligation on CLL cells caused increase of CD150 mRNA level that is a one of the EBF1 target genes. Conclusions: Analysis of TFs expression profile revealed upregulated SPIB mRNA level and downregulated PU.1 in CLL cells. CD150 and CD180 receptors may modulate transcriptional program in CLL cells by regulating the TFs expression levels.

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Factors involved in CLL pathogenesis and cell survival are disrupted by differentiation of CLL B-cells into antibody-secreting cells

Cited by 10 publications

References 94 publications

Chronic Lymphocytic Leukemia B-Cell Normal Cellular Counterpart: Clues From a Functional Perspective

Chronic Lymphocytic Leukemia B-Cell Normal Cellular Counterpart: Clues From a Functional Perspective

Wnt signalling pathways in chronic lymphocytic leukaemia and B‐cell lymphomas

Cd150 and Cd180 Are Involved in Regulation of Transcription Factors Expression in Chronic Lymphocytic Leukemia Cells

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