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The B-cell calcium sensor predicts progression of chronic lymphocytic leukemia

Leukemia volume 23, pages 426–429 (2009)Cite this article

Identifying mechanisms responsible for the clinical heterogeneity of chronic lymphocytic leukemia (CLL) is important to develop better treatments for this disease. Variations in responsiveness to immunoreceptor signaling may be responsible for differences in proliferation of CLL cells in vivo.1 Accordingly, we examined the status of the B-cell calcium sensor (CaoS) in primary CLL cells, as it responds to extracellular calcium (Cao2+) fluctuations by modulating subsequent signal transduction through immunoreceptors.2

As CLL patients could be classed into two groups, depending on the responsiveness of their tumor cells to Cao2+, CaoS status was correlated to other clinical parameters and conventional biological prognostic factors3 (Table 1). Strikingly, intact Cao2+-sensing was associated with increased Rai stage, serum β2-microglobulin levels, CD38 expression and need for treatment, along with significantly shorter lymphocyte doubling times (LDTs) (Table 1), all of which are markers of more aggressive disease.3 Increases in Cao2+ responsiveness over time were observed in the CLL cells of six patients, associated with changes in clinical course such as shorter lymphocyte doubling times (LDTs) and need to institute chemotherapy (not shown).

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Acknowledgements

This study was supported by the Ontario Institute of Cancer Research (OICR), Canadian Institutes of Health Research (CIHR), National Cancer Institute of Canada (NCIC) with funds from the Terry Fox Foundation, Leukemia and Lymphoma Society of Canada (to DS), and studentships from the Natural Sciences and Engineering Research Council of Canada (NSERC) (to CH) and NCIC (to JT).

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Authors and Affiliations

  1. Division of Molecular and Cellular Biology, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada

    C M Hammond, Y Shi, D White, D Cervi, J Tomic & D E Spaner

  2. Department of Medical Biophysics, University of Toronto, Toronto, Canada

    C M Hammond, J Tomic & D E Spaner

  3. Department of Medical Oncology, Sunnybrook Regional Cancer Center, Toronto, Canada

    D E Spaner

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  1. C M Hammond
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  2. Y Shi
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  3. D White
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  5. J Tomic
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  6. D E Spaner
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Correspondence to D E Spaner.

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Hammond, C., Shi, Y., White, D. et al. The B-cell calcium sensor predicts progression of chronic lymphocytic leukemia. Leukemia 23, 426–429 (2009). https://doi.org/10.1038/leu.2008.351

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