Tyrosine Kinase Targeted Treatment of Chronic Myelogenous Leukemia and Other Myeloproliferative Neoplasms

摘要: Myeloproliferative neoplasms (MPNs) include Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) and the Ph− diseases primary myelofibrosis (PMF), polycythemia vera (PV) essential thrombocythemia (ET). Since FDA approval of imatinib in 2001, CML treatment has been focused on tyrosine kinase inhibitors. With these targeted therapies, imatinib-resistant emerged as a major problem. Second generation inhibitors (TKIs) have allowed for effective some patients with resistance, but bcr-abl mutants such T315I remain problematic. Additional agents are development discussed here. New clinical issues TKI premature termination therapy due to adverse-effects, cost therapy, apparently indefinite duration who achieved complete molecular response (CMR). In contrast Ph+ CML, MPNs is novel less clear therapeutic potential. insights into alterations JAK-STAT signaling pathway, particularly mediated by JAK2 V617F mutation. The recent multiple provided hope rational management disorders. Recently, ruxolitinib was approved PMF. Current data suggests, however, that given its vital cell function, benefit targeting Jak kinases general, or specifically may be than derived from ABL-directed CML. This review focuses current options negative myeloproliferative limitations faced practice.