Hematologic Malignancies Chronic Myeloid Leukemia

© Touch MEdical MEdia 2014 97 Abstract Chronic myeloid leukemia (CML) is induced by the BCR-ABL oncogene. The advent of BCR-ABL tyrosine kinase inhibitors (TKIs) has redefined treatment goals in CML starting with imatinib and followed by the newer TKI inhibitors including dasatinib, nilotinib, bosutinib, and ponatinib. However, a significant proportion of patients do not achieve a satisfactory response to TKIs and resistance remains an unmet need in the in the treatment of CML. Furthermore, disease eradication with TKIs may pose a significant challenge: minimal residual disease (MRD) remains detectable following treatment with these agents. Recently, several new molecular targets have been proposed in CML, and several drugs are in clinical development. Omacetaxine, a protein translation inhibitor, has shown the potential to substantially reduce MRD in animal models and has demonstrated clinical activity in phase II clinical trials regardless of patients’ BCR-ABL T313I mutation status. The broad range of therapeutic effects associated with interferon may reduce resistance and relapse, and has resulted in a resurgence of interest in this therapy. In addition, several other therapeutic targets are currently undergoing clinical investigation.