Molecular mechanisms of resistance of leukemia to imatinib mesylate.
Despite high rates of hematologic and cytogenetic responses to imatinib therapy, the emergence of resistance to imatinib has been recognized as a major problem in the treatment of Ph-positive leukemia. The high frequency of BCR-ABL mutations and amplifications represents the high degree of heterogeneity in patients with advanced phase of CML, in whom multiple leukemic clones may exist. Therefore, a single inhibitor is unlikely to able to block all mutants.
Tauchi
Tetsuzo
T
First Department of Internal Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. tauchi@tokyo-med.ac.jp
Ohyashiki
Kazuma
K
D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics; D018740:Genetic Heterogeneity; D006801:Humans; D000068877:Imatinib Mesylate; D007938:Leukemia / Q000188:drug therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D009154:Mutation; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl