Philadelphia Chromosome-Negative Myeloproliferative Neoplasms

In the therapy of the Philadelphia chromosome (Ph)-negative chronic myeloproliferative neoplasms (MPNs)-essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF), hypereosinophilic syndrome/chronic eosinophilic leukemia (HES/CEL), and systemic mast cell disease (SMCD)-we are at an exciting cross-roads where, on the one hand, we are experiencing an explosive increase in our understanding of the pathogenetic mechanisms of these disorders and, on the other hand, we are witnessing rapid evolution of targeted therapies hoping to block these pathogenetic mechanisms. The increased understanding of the role of tyrosine kinases has led to efficacious targeted therapy in CEL and subsets of SMCD. The discovery of the JAK2-V617F and related mutations in ET, PV, and PMF have ushered a wave of investigation into novel tyrosine kinase inhibitors currently being investigated in clinical trials. Current management of each of these conditions requires a thoughtful consideration of prognosis and the risks and benefit of each therapeutic modality.