Polycythemia vera: diagnosis, clinical course, and current management

Abstract

Abstract: Very important developments related to polycythemia vera (PV) have occurred during the last two decades. The discoveryof Janus kinase (JAK) 2 mutations has changed both the diagnosis and clinical management of PV. Currently JAK2 molecular testingis essential in the diagnostic work-up and JAK2 mutation positivity is a major diagnostic criterion. The discovery of JAK2 mutationssuggested that abnormal JAK-STAT signaling was a pivotal feature in the pathogenesis of Philadelphia-negative myeloproliferativeneoplasms. This idea led to the development of JAK inhibitors. Currently ruxolitinib, a JAK1/JAK2 inhibitor, is also approved for PVpatients with hydroxyurea resistance or intolerance. International collaborations have made it possible to describe disease characteristicsand evolution better. Presently it is possible to quantify the symptomatic burden of the disease and to estimate prognosis. In spite ofthese developments, management of PV still largely depends on estimation of thromboembolic risk and trying to decrease the riskwith 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 managementalgorithm. The authors also point to still unresolved questions and unmet needs in diagnosis and management.