Abstract
The discovery of activating JAK2 mutations changed the landscape of MPN treatment dramatically, quickly prompting the development of small molecule inhibitors of JAK2. First-generation JAK inhibitors are ATP-competitive antagonists of the JAK kinase domain and each inhibits the activity of one or more JAK isoforms to different degrees. Ruxolitinib, a dual JAK1/2 inhibitor, was the first of its class to be approved for treatment of primary myelofibrosis (PMF) and post-PV/ET MF. Treatment with ruxolitinib has been shown to reduce spleen size and alleviate systemic symptoms of MF1, although the myelosuppressive effects of ruxolitinib, particularly anemia, are problematic for MF patients.
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