Clinical resistance to imatinib: mechanisms and implications.
Although responses to imatinib in chronic phase chronic myelogenous leukemia have been durable in most cases, most patients in advanced disease develop resistance and relapse after a short duration of therapy. The mechanisms of drug resistance are diverse, but in most cases, mutations are found at the time of resistance that change amino acids within the kinase domain of BCR-ABL. Cytogenetic and molecular analyses at the time of resistance are suggested to guide therapy.
Hochhaus
Andreas
A
III. Medizinische Klinik, Fakultät für Klinische Medizin Mannheim, Universität Heidelberg, Wiesbadener Strasse 7-11, 68305 Mannheim, Germany. hochhaus@uni-hd.de
Hughes
Timothy
T
D001549:Benzamides; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy*; D009154:Mutation; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl