title: CD40 stimulation sensitizes CLL cells to rituximab-induced cell death.
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.
authors.affiliation: Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands. m.jak@amc.uva.nl
authors.forename: M
authors.initials: M
authors.lastname: Jak
authors.forename: G G W
authors.initials: GG
authors.lastname: van Bochove
authors.forename: R A W
authors.initials: RA
authors.lastname: van Lier
authors.forename: E
authors.initials: E
authors.lastname: Eldering
authors.forename: M H J
authors.initials: MH
authors.lastname: van Oers
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D000970:Antineoplastic Agents; D019013:CD40 Antigens / Q000378:metabolism*; D002118:Calcium; D016923:Cell Death / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000069283:Rituximab; D014407:Tumor Cells, Cultured
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D019013:CD40 Antigens; D017382:Reactive Oxygen Species; D000069283:Rituximab; D002118:Calcium