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Chronic Lymphocytic Leukemia

CD40 stimulation sensitizes CLL cells to rituximab-induced cell death

Leukemia volume 25, pages 968–978 (2011)Cite this article

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Abstract

In vitro CD40-stimulated chronic lymphocytic leukemia (CLL) cells are resistant to cytotoxic drugs. In sharp contrast, we here show that CD40 stimulation sensitizes CLL cells to rituximab-mediated cell death. This increased sensitivity is specific for anti-CD20 treatment. Rituximab-mediated death in CD40-stimulated CLL cells shows rapid kinetics (within hours), and is caspase and p53 independent, but depends on extracellular Ca2+ and reactive oxygen species (ROS) production. By increasing basal ROS production, CD40 stimulation sensitizes CLL cells to rituximab-mediated death. Our findings provide a rationale for combination treatment of CLL with cytotoxic drugs and anti-CD20 monoclonal antibodies.

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Acknowledgements

We are indebted to our patients for their commitment to this study. We would like to thank Peter Teeling from the Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands, for his kind help with electron microscopy, Berend Hooibrink from the Department of Cell Biology, Academic Medical Center, Amsterdam for his assistance on the FACS Vantage SE in the Ca2+ flux experiments and Dr Meijer from the Department of Medical Biochemistry, Academic Medical Center, Amsterdam, for his help in the autophagy experiments.

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  1. Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands

    M Jak, G G W van Bochove & M H J van Oers

  2. Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands

    R A W van Lier & E Eldering

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  1. M Jak
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  3. R A W van Lier
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Correspondence to M Jak.

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Jak, M., van Bochove, G., van Lier, R. et al. CD40 stimulation sensitizes CLL cells to rituximab-induced cell death. Leukemia 25, 968–978 (2011). https://doi.org/10.1038/leu.2011.39

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