The oncologist
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Chronic myelogenous leukemia (CML) is defined by the presence of the constitutively active tyrosine kinase breakpoint cluster region/Abelson (Bcr-Abl), which activates numerous signal transduction pathways leading to uncontrolled cell proliferation. The development of the Bcr-Abl-targeted imatinib represents a paradigm shift in the treatment of CML, because treatment with imatinib resulted in significantly better patient outcome, response rates, and overall survival compared with previous standards. Despite this advance, not all patients benefit from imatinib because of resistance and intolerance. ⋯ A large trial program showed that dasatinib is effective in patients previously exposed to imatinib and has a manageable safety profile in all phases of CML and Philadelphia chromosome-positive acute lymphoblastic leukemia, resulting in its approval. Nilotinib, an analogue of imatinib, also has demonstrated activity in a similar patient population. These agents and less clinically advanced strategies are discussed in this review.