Polycythemia vera: diagnosis, clinical course, and current management

Very important developments related to polycythemia vera (PV) have occurred during the last two decades. The discovery of Janus kinase (JAK) 2 mutations has changed both the diagnosis and clinical management of PV. Currently JAK2 molecular testing is essential in the diagnostic work-up and JAK2 mutation positivity is a major diagnostic criterion. The discovery of JAK2 mutations suggested that abnormal JAK-STAT signaling was a pivotal feature in the pathogenesis of Philadelphia-negative myeloproliferative neoplasms. This idea led to the development of JAK inhibitors. Currently ruxolitinib, a JAK1/JAK2 inhibitor, is also approved for PV patients with hydroxyurea resistance or intolerance. International collaborations have made it possible to describe disease characteristics and evolution better. Presently it is possible to quantify the symptomatic burden of the disease and to estimate prognosis. In spite of these developments, management of PV still largely depends on estimation of thromboembolic risk and trying to decrease the risk with or without cytoreductive medications. Different approaches have been proposed by international disease experts for the diagnosis, thromboembolic risk estimation, and drug selection. This paper aims to review clinical aspects of PV and propose a management algorithm. The authors also point to still unresolved questions and unmet needs in diagnosis and management.