Basal [Ca.sup.2+] signaling is particularly increased in mutated chronic lymphocytic leukemia

Basal [Ca.sup.2+] signaling is particularly increased in mutated chronic lymphocytic leukemia

On the basis of somatic hypermutation status of their B-cell antigen receptor (BCR) genes, chronic lymphocytic leukemia (CLL) patients can be divided into unmutated CLL (U-CLL) or mutated CLL (M-CLL). Approximately 30% of CLL patients express a stereotypic BCR, which may indicate that specific antig...

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Bibliographic Details
Published in:Leukemia p. 321
Main Authors: Muggen, A.F, Pillai, S.Y, Kil, L.P, van Zelm, M.C, van Dongen, J.J.M, Hendriks, R.W, Langerak, A.W
Format: Journal Article
Language:English
Published: Nature Publishing Group 01-02-2015
Subjects:
Antigenic determinants
Care and treatment
Chronic lymphocytic leukemia
Gene mutations
Genetic aspects
Health aspects
Physiological aspects
Netherlands
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Summary:On the basis of somatic hypermutation status of their B-cell antigen receptor (BCR) genes, chronic lymphocytic leukemia (CLL) patients can be divided into unmutated CLL (U-CLL) or mutated CLL (M-CLL). Approximately 30% of CLL patients express a stereotypic BCR, which may indicate that specific antigenic stimulation is driving CLL pathogenesis. Recently, it was reported that BCRs from CLL cells are capable of antigen-independent, cell-autonomous signaling, through recognition of an internal framework 2 (FR2) BCR epitope. We hypothesized that the level of cell-autonomous signaling may differ between CLL subgroups. Therefore, we analyzed [Ca.sup.2+] signaling in a series of primary stereotypic or heterogeneous U-CLL and M-CLL (n = 68) and healthy controls (n = 14). We confirmed that basal [Ca.sup.2+] signaling in CLL cells is higher than in normal B cells. Interestingly, we found that basal signaling was particularly increased in M-CLL. The degree of basal signaling did not correlate with membrane immunoglobulin levels, HCDR3 characteristics or FR2/FR3 sequence. We conclude that the level of basal [Ca.sup.2+] signaling is not uniformly enhanced in CLL B cells, but is associated with CLL immunoglobulin heavy chain V mutational status, reflecting a distinct cellular origin and possibly a different anergic state induced by repetitive or continuous antigen binding in vivo. Leukemia (2015) 29, 321-328; doi: 10.1038/leu.2014.188
ISSN:0887-6924
DOI:10.1038/leu.2014.188