Polycythemia Vera: An Appraisal of the Biology and Management 10 Years After the Discovery of JAK2 V617F

Abstract

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm that is associated with a substantial symptom burden, thrombohemorrhagic complications, and impaired survival. A decade after the seminal discovery of an activating mutation in the tyrosine kinase JAK2 in nearly all patients with PV, new treatment options are finally beginning to emerge, necessitating a critical reappraisal of the underlying pathogenesis and therapeutic modalities available for PV. Herein, we comprehensively review clinical aspects of PV including diagnostic considerations, natural history, and risk factors for thrombosis. We summarize recent studies delineating the genetic basis of PV, including their implications for evolution to myelofibrosis and secondary acute myeloid leukemia. We assess the quality of evidence to support the use of currently available therapies, including aspirin, phlebotomy, hydroxyurea, and interferon. We analyze recent studies evaluating the safety and efficacy of JAK inhibitors, such as ruxolitinib, and evaluate their role in the context of other available therapies for PV. This review provides a framework for practicing hematologists and oncologists to make rational treatment decisions for patients with PV.