Purpose of review
Myelodysplastic/myeloproliferative neoplasms (MDS/MPNs), including chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, MDS/MPN-Unclassifiable, ring sideroblasts associated with marked thrombocytosis, and juvenile myelomonocytic leukemia, are clonal hematologic diseases characterized by myeloid dysplasia, proliferation, and absence of the molecular lesions BCR/ABL, PDGFRA, PDGFRB, and FGFR1. There are currently no US Food and Drug Administration approved therapies for all MDS/MPN subtypes. Advances in the understanding of the biologic and molecular drivers of these diseases will help in diagnosis, prognosis, and therapeutics. This review article summarizes the molecular aspects of MDS/MPNs and provides an overview of classic and emerging therapies.
Next generation sequencing has provided new insights into the genetic nature of MDS/MPNs. Molecular mutations such as TET2, CBL, SETBP1, CSF3R, and SF3B1 are relevant as diagnostic and prognostic biomarkers. Hematopoietic cell transplantation, although potentially curative, is applicable to only a small proportion of patients. Attempts to standardize response and outcomes criteria specific to MDS/MPN and clinical trials using novel agents focused on MDS/MPN patients are underway.
MDS/MPNs have clinicopathologic features of both MDS and MPN diseases. Emerging molecular data support the distinctive disease biology of each of these morphologic entities, and will serve as the foundation to develop effective therapeutics that can ameliorate disease-related complications and lead to better outcomes.