Validating Aurora Kinase A as a therapeutic target for MPNs

Myeloproliferative neoplasms (MPNs) comprise a group of blood cancers with excessive production of different kinds of blood cells, which include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). Polycythemia vera is characterized by a dramatic increase of red blood cells. In essential thrombocythemia, there is a significant increase of platelets in the blood. Primary myelofibrosis is characterized by replacement of bone marrow cells by connective tissues. In myelofibrosis, megakaryocytes, the cells that make platelets, fail to undergo differentiation and secret substances stimulating replacement of bone marrow cells by connective tissues. JAK2 kinase is an important gene regulating the development of different kinds of blood cells. Mutation in JAK2, which causes over-activation of JAK2 kinase, was identified in the majority of patients with polycythemia vera and in about half of the patients with essential thrombocythemia and primary myelofibrosis. Several JAK2 kinase inhibitors have been tested in clinical trials for myeloproliferative neoplasms. But none of JAK2 inhibitors offer clinical remission or cure. Other therapies for myeloproliferative neoplasms are also inadequate. Therefore, there is an urgent need for novel therapies for patients with myeloproliferaive neoplasms.