Why doesn't imatinib cure chronic myeloid leukemia?

Imatinib mesylate has transformed the treatment for chronic myeloid leukemia (CML). The vast majority of patients obtain hematologic remission, with a low probability of progression of disease. Yet imatinib rarely cures CML, and current recommendations dictate lifelong treatment with imatinib. In this review we analyze the biology behind the failure of imatinib to fully eradicate CML. We review evidence that indicates that the leukemic stem cell for CML is inherently resistant to imatinib, and that imatinib treatment itself may enhance this resistance.