Down‐regulation of CD5 mRNA in B‐chronic lymphocytic leukemia cells by differentiation‐inducing agents

Sm, Gignac; Buschle, Michael; Av, Hoffbrand; Drexler, Helmut

doi:10.1002/eji.1830200526

Cited by 6 publications

(2 citation statements)

References 22 publications

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“…This study supports a hypothesis that CD5 state switching is likely to occur as a common event and continuous switching may occur, although not at an equal frequency as CD5 high /CD5 low ratios in CLL do not tend to 1. Decreased CD5 expression corresponds with the normal development of B cells to plasma cells [21] and it is possible that the CD5 low CLL population represents further differentiated CLL subclones.…”

Section: Resultsmentioning

confidence: 99%

Dynamic variation of CD5 surface expression levels within individual chronic lymphocytic leukemia clones

Bashford-Rogers

Palser

Hodkinson

et al. 2017

Experimental Hematology

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Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of clonally derived mature CD5high B cells; however, the cellular origin of CLL is still unknown. Patients with CLL also harbor variable numbers of CD5low B cells, but the clonal relationship of these cells to the bulk disease is unknown and can have important implications for monitoring, treating, and understanding the biology of CLL. Here, we use B-cell receptors (BCRs) as molecular barcodes to first show by single-cell BCR sequencing that the great majority of CD5low B cells in the blood of CLL patients are clonally related to CD5high CLL B cells. We investigate whether CD5 state switching was likely to occur continuously as a common event or as a rare event in CLL by tracking somatic BCR mutations in bulk CLL B cells and using them to reconstruct the phylogenetic relationships and evolutionary history of the CLL in four patients. Using statistical methods, we show that there is no parsimonious route from a single or low number of CD5low switch events to the CD5high population, but rather, large-scale and/or dynamic switching between these CD5 states is the most likely explanation. The overlapping BCR repertoires between CD5high and CD5low cells from CLL patient peripheral blood reveal that CLL exists in a continuum of CD5 expression. The major proportion of CD5low B cells in patients are leukemic, thus identifying CD5low B cells as an important component of CLL, with implications for CLL pathogenesis, clinical monitoring, and the development of anti-CD5-directed therapies.

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Section: Resultsmentioning

confidence: 99%

Dynamic variation of CD5 surface expression levels within individual chronic lymphocytic leukemia clones

Bashford-Rogers

Palser

Hodkinson

et al. 2017

Experimental Hematology

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“…However, remarkable results were obtained with a phorbol diester, phorbol myristate acetate (PMA). This molecule has been shown to induce differentiation and activation of CLL cells into ASPCs ( 22 , 194 , 236 – 238 , 241 ) [reviewed in Ref. ( 242 )], suggesting a critical role for the protein kinase C (PKC) pathway in the activation and differentiation of CLL B-cells (see below).…”

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

confidence: 99%

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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Biosynthetic Products for Anticancer Drug Design and Treatment: The Bryostatins

Pettit

Herald

Hogan

2002

Anticancer Drug Development

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Down‐regulation of CD5 mRNA in B‐chronic lymphocytic leukemia cells by differentiation‐inducing agents

Cited by 6 publications

References 22 publications

Dynamic variation of CD5 surface expression levels within individual chronic lymphocytic leukemia clones

Dynamic variation of CD5 surface expression levels within individual chronic lymphocytic leukemia clones

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

Biosynthetic Products for Anticancer Drug Design and Treatment: The Bryostatins

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