[Myeloproliferative diseases caused by JAK2 mutation]

Polycythemia vera (PV), essential thrombocythemia(ET), and primary myelofibrosis (PMF) share common clinical features, being clonal disorders of multipotent progenitors. In 2005, a somatic activating mutation in JAK2 (V617F) was identified in most patients with PV and in about half of patients with ET or PMF. The JAK2 mutation causes the constitutive activation of the JAK-STAT signaling pathway, and leads to autonomous cell growth in a cytokine-independent manner. A higher expression of JAK2 V617F would favor erythrocytosis, and a lower one would favor thrombocytosis. This may suggest that the expression levels of JAK2 V617F directly determine which cell lineages increase, possibly leading to the diversity of myeloproliferative diseases. Although only V617F JAK2 may cause myeloproliferative disease (MPD), clonogenic assay, analysis of familial MPD patients, and examination of JAK2 mutation in acute leukemia patients transformed from MPD show that there are additional somatic mutations which contribute to the pathogenesis of V617F JAK2 positive PV, ET, and PMF.