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JOURNAL ARTICLE
REVIEW
The BCR-ABL1-negative myeloproliferative neoplasms: a review of JAK inhibitors in the therapeutic armamentarium.
Expert Opinion on Pharmacotherapy 2017 December
INTRODUCTION: The classical BCR-ABL1-negative myeloproliferative neoplasms (MPN) include primary myelofibrosis (PMF), polycythemia vera (PV) and essential thrombocythemia (ET). They are characterized by stem cell-derived clonal proliferation, harbor Janus kinase 2 (JAK2), or calreticulin (CALR), or myeloproliferative leukemia virus oncogene (MPL) driver mutations and exert an over activated JAK-signal transducer and activator of transcription (STAT) pathway. Therefore JAK inhibiting strategies have been successfully investigated in MPN clinical trials. Areas covered: The present review aims to provide a concise overview of the current and future role of JAK inhibitors in the therapeutic armamentarium of MPN. Expert opinion: The JAK1/JAK2 inhibitor ruxolitinib has clearly enriched the therapeutic armamentarium of MPN and is now licenced for more than five years in MF and over three years as second line in PV. Momelotinib, although of limited activity in MPN trials, demonstrated unique property of improving MF associated anemia. Less myelosuppressive or more selective JAK inhibitors like pacritinib, NS-01872 or Itacitinib are new promising agents tested in MF. JAK inhibition has become a cornerstone of MPN therapy and future efforts focus on ruxolitinib-based combinations and new JAK inhibitors.
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