Title:Biology and Clinical Management of Myeloproliferative Neoplasms and Development of the JAK Inhibitor Ruxolitinib
Volume: 19
Issue: 26
Author(s): J. Mascarenhas, T. I. Mughal and S. Verstovsek
Affiliation:
Keywords:
Essential thrombocythemia, janus kinase, JAK inhibitor, JAK-STAT, myelofibrosis, myeloproliferative neoplasms, polycythemia vera, primary myelofibrosis, quality of life, ruxolitinib, splenomegaly, symptoms.
Abstract: Myeloproliferative neoplasms (MPN) are debilitating stem cell-derived clonal myeloid malignancies. Conventional treatments
for the BCR-ABL1-negative MPN including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF)
have, so far, been unsatisfactory. Following the discovery of dysregulated JAK-STAT signaling in patients with MPN, many efforts have
been directed toward the development of molecularly targeted therapies, including inhibitors of JAK1 and JAK2. Ruxolitinib (previously
known as INCB018424; Incyte Corporation, Wilmington, Delaware, USA) is a rationally designed potent oral JAK1 and JAK2 inhibitor
that has undergone clinical trials in patients with PV, ET, and PMF. Ruxolitinib was approved on November 16, 2011 by the United
States Food and Drug Administration for the treatment of intermediate or high-risk myelofibrosis (MF), including patients with PMF,
post-PV MF, and post-ET MF. In randomized phase III studies, ruxolitinib treatment resulted in significant and durable reductions in
splenomegaly and improvements in disease-related symptoms in patients with MF compared with placebo or best available therapy. The
most common adverse events were anemia and thrombocytopenia, which were manageable and rarely led to discontinuation. This review
addresses the cellular and molecular biology, and the clinical management of MPN.
