Secondary acute myeloid leukemias arising from Philadelphia chromosome negative myeloproliferative neoplasms: pathogenesis, risk factors, and therapeutic strategies

Abstract

The classic Philadelphia chromosome negative myeloproliferative neoplasms including primary myelofibrosis, polycythemia vera, and essential thrombocythemia are associated with a variable propensity for transformation into acute myeloid leukemia. Leukemic transformation in these disorders, so called MPN-blast phase, is uniformly associated with a poor prognosis. In recent years, there has been an increasing understanding of the molecular complexity underlying Philadelphia chromosome negative myeloproliferative neoplasms (Ph- MPNs), and this has spurred efforts to investigate the molecular risk factors associated with clinical outcome in these disorders, including the risk of leukemic transformation. At the same time, there is an ongoing and significant need for new approaches which have the potential to change the natural history of these disorders. This review will focus on the risk factors associated with the development of MPN in blast phase (MPN-BP) including clinical and molecular risk factors, current treatment strategies, and emerging investigational approaches.