Advances in the understanding and management of primary myelofibrosis

Identification of the JAK2V617F mutation in 2005 boosted basic and clinical research in primary myelofibrosis (PMF) and other Philadelphia-negative chronic myeloproliferative neoplasms. We herein review the recent contributions to the understanding and management of PMF.

In addition to the JAK2V617F mutation, different genetic markers have recently been discovered in PMF, the most relevant ones being the mutations in the thrombopoietin (MPL), TET2, and EZH2 genes. From the clinical point of view, attention has recently been paid to thrombosis as a relevant complication of PMF and new prognostic models for this disease have been created and refined. Regarding therapy, reduced intensity conditioning regimens have allowed the possibility of performing allogeneic stem cell transplantation in older PMF patients, whereas the first clinical trials with JAK2 inhibitors have shown their efficacy in splenomegaly and constitutional symptoms.

The molecular biology of PMF is more complex than initially believed. Due to its associated mortality risk, stem cell transplantation should be restricted to patients with poor prognostic features. The JAK2-inhibitors are promising as a palliative treatment of PMF. In conclusion, the once neglected PMF has become a very active field of research, which will hopefully soon translate into relevant therapeutic advances.