期刊
LEUKEMIA
卷 25, 期 6, 页码 968-978出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2011.39
关键词
chronic lymphocytic leukemia; anti-CD20; cell death; CD40 stimulation
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. Leukemia (2011) 25, 968-978; doi:10.1038/leu.2011.39; published online 15 March 2011
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