Kinase Inhibitors in the Treatment of Myeloid Malignancies

Aberrant signaling pathway activation is a central feature of myeloid malignancies. With the development of the tyrosine kinase inhibitor, imatinib, to treat chronic myelogenous leukemia (CML), the paradigm of targeted therapy in cancer was established. Imatinib inhibits ABL, KIT, and platelet-derived growth factor receptor signaling and as a result is approved for the treatment of CML and subsets of patients with systemic mastocytosis (SM) and hypereosinophilic syndrome. Activated JAK-STAT signaling is central to the pathogenesis of BCR-ABL-negative myeloproliferative neoplasms (MPN), and the JAK1/2 inhibitor, ruxolitinib, is approved for the treatment of myelofibrosis and polycythemia vera.

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