How I treat the blast phase of Philadelphia chromosome-negative myeloproliferative neoplasms

Abstract

The classic Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematopoietic stem-cell diseases, characterized by activated JAK/STAT signaling and significant phenotypic mimicry, including a propensity for evolution to myeloid blast phase disease. Effective therapeutic options are limited for patients with Ph^- MPNs in the blast phase (MPN-BP), and allogeneic stem-cell transplantation is the only known cure. Our increasing understanding of the molecular pathogenesis of this group of diseases, coupled with the increasing availability of targeted agents, has the potential to inform new subset-specific therapeutic approaches. Ultimately, progress in MPN-BP will hinge on prospective clinical and translational investigations with the goal of generating more effective treatment interventions. This case-based review highlights the molecular and clinical heterogeneities of MPN-BP and incorporates a treatment algorithm that underscores the importance of a personalized approach to this challenging group of diseases.