Turning the tide in myelodysplastic/myeloproliferative neoplasms

Nat Rev Cancer. 2017 Jun 23;17(7):425-440. doi: 10.1038/nrc.2017.40.


Myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) are aggressive myeloid malignancies recognized as a distinct category owing to their unique combination of dysplastic and proliferative features. Although current classification schemes still emphasize morphology and exclusionary criteria, disease-defining somatic mutations and/or germline predisposition alleles are increasingly incorporated into diagnostic algorithms. The developing picture suggests that phenotypes are driven mostly by epigenetic mechanisms that reflect a complex interplay between genotype, physiological processes such as ageing and interactions between malignant haematopoietic cells and the stromal microenvironment of the bone marrow. Despite the rapid accumulation of genetic knowledge, therapies have remained nonspecific and largely inefficient. In this Review, we discuss the pathogenesis of MDS/MPN, focusing on the relationship between genotype and phenotype and the molecular underpinnings of epigenetic dysregulation. Starting with the limitations of current therapies, we also explore how the available mechanistic data may be harnessed to inform strategies to develop rational and more effective treatments, and which gaps in our knowledge need to be filled to translate biological understanding into clinical progress.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antineoplastic Agents / therapeutic use
  • Child
  • DNA Methylation
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Genotype
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Inflammation / complications
  • Molecular Targeted Therapy
  • Mutation
  • Myelodysplastic-Myeloproliferative Diseases / epidemiology
  • Myelodysplastic-Myeloproliferative Diseases / genetics*
  • Myelodysplastic-Myeloproliferative Diseases / therapy*
  • Phenotype
  • Prognosis
  • Signal Transduction / drug effects


  • Antineoplastic Agents