New Advances In Molecular Pathogenesis And Diagnosis Of Essential Thrombocythemia

Essential thrombocythemia (ET), a subtype of myeloproliferative neoplasm (MPN), is a hematopoietic disorder that is characterized clinically by thrombocytosis which results from bone marrow megakaryocyte hyperplasia. Patients with ET are at increased risk for developing thrombosis, hemorrhage, myelofibrosis and transformation to acute myeloid leukemia. The molecular pathogenesis of ET largely remains to be fully understood but the identification of the JAK2V617F mutation in more than half of ET patients was a major improvement in our understanding of this disease and may represent the first biologic marker useful for risk stratification and diagnosis.But there is still a subset of patients with JAK2V617F-negative ET, and some of these patients have been identified gain-of-function mutations in the thrombopoietin receptor (MPL) in subsequent studies. Since the discovery of JAK2V617F is an important advance in our understanding of the molecular pathogenesis of ET, WHO revised the diagnostic criteria for ET, which lowered the platelet threshold for a diagnosis of ET to 450 x 109/L, and allows JAK2V617F detection to demonstrate the presence of a clonal MPN, but still requires clinicians to exclude a diagnosis of polycythemia vera (PV), primary myelofibrosis( PMF), chronic myelogenous leukemia (CML) or orther MPN based on clinical, laboratory, and pathologic data. As the pathogenesis of JAK2/MPL mutations are both related with the activation of JAK-STAT signaling transduction pathway, specific inhibitors of JAK2 kinase activity have been designed and have entered clinic trials.