The role of DNA repair in chronic lymphocytic leukemia pathogenesis and chemotherapy resistance.
Front-line therapy for chronic lymphocytic leukemia (CLL) with alkylating agents is associated with low rates of complete remission and no improvement in overall survival. The ability of CLL cells to efficiently repair alkylator-induced damage to DNA might explain this lack of response. Novel strategies that inhibit DNA repair, such as combinations of alkylating agents, purine nucleoside analogues, and immunotherapy, have produced durable clinical and molecular remission in both untreated and relapsed CLL. This review evaluates the contribution of DNA repair processes in the development of resistance to chemotherapy and the impact of therapies that exploit the DNA repair capacity of CLL cells to therapeutic advantage.
Sampath
Deepa
D
Department of Experimental Therapeutics, Unit 71, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. dsampath@mdanderson.org
Plunkett
William
W
D000477:Alkylating Agents / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004260:DNA Repair / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics*
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm
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