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Chronic Lymphocytic Leukemia

Basal Ca2+ signaling is particularly increased in mutated chronic lymphocytic leukemia

Leukemia volume 29, pages 321–328 (2015)Cite this article

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Abstract

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 Ca2+ 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 Ca2+ 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 Ca2+ 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.

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Acknowledgements

We thank Marjolein de Bruijn for helpful discussions.

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Authors and Affiliations

  1. Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    A F Muggen, M C van Zelm, J J M van Dongen & A W Langerak

  2. Department of Pulmonary Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    S Y Pillai, L P Kil & R W Hendriks

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  1. A F Muggen
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Correspondence to A W Langerak.

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Muggen, A., Pillai, S., Kil, L. et al. Basal Ca2+ signaling is particularly increased in mutated chronic lymphocytic leukemia. Leukemia 29, 321–328 (2015). https://doi.org/10.1038/leu.2014.188

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