Janus Kinase Mutations

Abstract

The chronic myeloproliferative neoplasms (MPNs) polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (MF) are commonly associated with mutations in the Janus kinase gene JAK2. A hallmark of PV is an abundance of red blood cells; ET, too many platelets; and MF, accumulation of neutrophils and monocytes accompanied by bone marrow fibrosis and bone marrow failure. Although knowledge of PV, ET, and MF has expanded considerably in the last decade, the pathophysiology behind these disorders is complex, and some of the underlying mechanisms are still unknown. The knowledge gap for these diseases has been compounded by the observation that a subset of patients with PV, ET, and MF do not present with mutations that activate JAK2. Recent studies suggest JAK inhibitors may offer significant benefit to patients with these MPNs and may have a role in the treatment of other malignancies that are also driven, at least in part, by activation of JAK signaling. However, additional genetic and functional studies are needed to identify the patients that will benefit most from JAK kinase inhibitors.