Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia

Recent insights into the molecular mechanisms of polycythemia vera (PV) and essential thrombocythemia (ET) are challenging the traditional diagnostic classification of these myeloproliferative disorders (MPDs). Clonality analysis using X-chromosome inactivation patterns has revealed apparent heterogeneity among the MPDs. The recently discovered single somatic activating point mutation in the JAK2 gene (JAK2-V617F) is found in the great majority of patients with PV, but also in many patients with phenotypically classified ET and other MPDs. In contrast to the acquired MPDs, mutations of the erythropoietin receptor and thrombopoietin receptor have been identified in familial forms of nonclonal erythrocytosis and thrombocytosis, respectively. The mechanisms of major clinical complications of PV and ET remain poorly understood. Quantitative or qualitative abnormalities of red cells and platelets do not provide clear explanations for the thrombotic and bleeding tendency in these MPDs, suggesting the need for entirely new lines of research in this area. Recently reported randomized clinical trials have demonstrated the efficacy and safety of low-dose aspirin in PV, and an excess rate of arterial thrombosis, major bleeding, and myelofibrotic transformation, but decreased venous thrombosis, in patients with ET treated with anagrelide plus aspirin compared to hydroxyurea plus aspirin.