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.