The role of the thrombopoietin receptor MPL in myeloproliferative neoplasms: recent findings and potential therapeutic applications

Abstract

Introduction: Classical Myeloproliferative Neoplasms (MPNs) include three disorders: Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF). MPNs are associated with constitutive activation of JAK2 leading to persistent cell signaling downstream of the dimeric myeloid cytokine receptors due to mutations in three genes encoding JAK2, calreticulin (CALR) and the thrombopoietin (TPO) receptor (MPL or TPOR). CALR and MPL mutants induce JAK2 activation that depends on MPL expression, thus explaining why they induce megakaryocyte pathologies including ET and PMF, but not PV. In contrast, JAK2 V617F drives all three diseases as it induces persistent signaling via EPO..