• Alex Ganetsky.
• Pharmacy Department, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. alex.ganetsky@gmail.com
• Pharmacotherapy. 2013 Jan 1; 33 (1): 84-92.

AbstractMyelofibrosis is a myeloproliferative neoplasm characterized by bone marrow fibrosis and extramedullary hematopoiesis. Evolution of myelofibrosis can lead to life-threatening complications, including transformation to leukemia, thrombotic events, and hemorrhagic episodes. The only curative therapy for myelofibrosis is allogeneic hematopoietic stem cell transplantation. Because this disease manifests primarily in the older population, many patients diagnosed with myelofibrosis are not considered medically fit for such aggressive therapy. Other available medical therapies do not halt disease progression; instead, current treatment strategies have focused on targeting specific symptomology, although with limited efficacy. The lack of effective treatment options for patients with myelofibrosis has rendered this orphan disease state an unmet medical need, and novel approaches to improve outcomes are necessary. Emerging research has identified numerous molecular mutations in patients with myelofibrosis, making this disease a potential candidate for molecularly targeted therapy. The most prevalent mutation identified is a gain-of-function mutation in the Janus kinase (JAK) family, JAK2 V617F, which has been identified in more than half of patients with myelofibrosis. This mutation results in a constitutively active JAK-signal transducer and activator of transcription pathway resulting in dysregulated cellular proliferation and hematopoiesis. Ruxolitinib is a small-molecule inhibitor of JAK1 and JAK2 and recently became the first drug approved by the United States Food and Drug Administration for the treatment of symptomatic intermediate- or high-risk myelofibrosis. In clinical trials, ruxolitinib demonstrated promising efficacy in reducing splenomegaly and myelofibrosis-related symptoms. However, ruxolitinib did not demonstrate disease-modifying potential and is not considered a curative therapeutic option. Adverse events associated with ruxolitinib are primarily hematologic, with thrombocytopenia and anemia being the most common toxicologic events identified. Future research will shed light on whether ruxolitinib in combination with other treatments will further enhance outcomes in myelofibrosis.© 2013 Pharmacotherapy Publications, Inc.

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