CD40 stimulation sensitizes CLL cells to rituximab-induced cell death

被引：25

作者：

Jak, M. ^{[1
,2
]}

van Bochove, G. G. W. ^{[1
]}

van Lier, R. A. W. ^{[2
]}

Eldering, E. ^{[2
]}

van Oers, M. H. J. ^{[1
]}

机构：

[1] Univ Amsterdam, Acad Med Ctr, Dept Hematol, NL-1105 AZ Amsterdam, Netherlands

[2] Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, NL-1105 AZ Amsterdam, Netherlands

来源：

LEUKEMIA | 2011年 / 25卷 / 06期

关键词：

chronic lymphocytic leukemia; anti-CD20; cell death; CD40; stimulation; CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELLS; MONOCLONAL-ANTIBODY; DOWN-REGULATION; HLA-DR; CD20; APOPTOSIS; LYMPHOMA; EXPRESSION; KINASE;

D O I：

10.1038/leu.2011.39

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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

引用

页码：968 / 978

页数：11

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