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- Title
CD40 stimulation sensitizes CLL cells to rituximab-induced cell death.
- Authors
Jak, M.; van Bochove, G. G. W.; van Lier, R. A. W.; Eldering, E.; van Oers, M. H. J.
- 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.
- Subjects
CHRONIC lymphocytic leukemia; RITUXIMAB; ANTINEOPLASTIC agents; CELL death; REACTIVE oxygen species; ENZYME activation; TREATMENT effectiveness; GENETICS
- Publication
Leukemia (08876924), 2011, Vol 25, Issue 6, p968
- ISSN
0887-6924
- Publication type
Article
- DOI
10.1038/leu.2011.39