Research advances in the role of JAK2 mutations in acute leukemia

Abstract:

The Janus kinase -signal transducer and activator of transcription (JAK-STAT) pathway plays pivotal roles in the regulation of cell proliferation, differentiation, migration and apoptosis, which is closely related with the development of hematopoietic cells and some hematological diseases. As an important signaling axis in JAK-STAT pathway, abnormally activated JAK2-STAT signaling is involved in the development of the hematological malignancies. JAK2V617F mutation is the important molecular pathogenesis of myeloproliferative disorders. Recent studies have demonstrated that JAK2 mutations are present in different acute leukemia subtypes and the frequency of mutations is different and that JAK2 mutations might be closely correlated with acute leukemia formation, treatment and prognosis. The pathogenic mechanism of JAK2 mutations has not been completely elucidated. JAK2 mutations might lead to JAK-STAT overactivation, resulting in the excessive proliferation, apoptosis resistance and differentiation blocking of blood cells. JAK2 inhibitors have been rapidly developed as targeted therapies for hematological disorders with JAK2 mutations. This article mainly focuses on recent studies about the role of JAK2 mutations in the pathogenesis, clinical characteristics and targeted therapies of acute leukemia.