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Leukemia. 2011 Jun;25(6):968-78. doi: 10.1038/leu.2011.39. Epub 2011 Mar 15.

CD40 stimulation sensitizes CLL cells to rituximab-induced cell death.

Author information

1
Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands. m.jak@amc.uva.nl

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 Ca(2+) 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.

PMID:
21403646
DOI:
10.1038/leu.2011.39
[Indexed for MEDLINE]

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