Advances in targeted therapy for chronic myeloid leukemia.

Despite the lack of long-term survival data, the impressive results obtained with imatinib mesylate (Gleevec) therapy and the lack of serious adverse events have significantly altered the management of patients with chronic myeloid leukemia. Nevertheless, a large proportion of patients with more advanced disease will develop resistance to imatinib mesylate monotherapy. To prevent the development of resistance, an understanding of the pathophysiology of chronic myeloid leukemia, including the signaling pathways that are activated by the BCR-ABL fusion protein, and the mechanisms of resistance to imatinib are required. This review summarizes the pathogenesis of chronic myeloid leukemia and the potential therapeutic impact of small molecule inhibitors that target pathways critical to the growth or survival of the leukemic cells in patients with chronic myeloid leukemia.