학술논문
CD40 stimulation sensitizes CLL cells to rituximab-induced cell death.
Document Type
Article
Source
Subject
*CHRONIC lymphocytic leukemia
*RITUXIMAB
*ANTINEOPLASTIC agents
*CELL death
*REACTIVE oxygen species
*ENZYME activation
*TREATMENT effectiveness
*GENETICS
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Language
ISSN
0887-6924
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. [ABSTRACT FROM AUTHOR]