Insight into the molecular pathophysiology of myelodysplastic syndromes: targets for novel therapy.

Journal Article (Review)

Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by abnormal cellular differentiation and maturation with variable progression to acute leukemia. Over the last decade, scientific discoveries have unraveled specific pathways involved in the complex pathophysiology of MDS. Prominent examples include aberrations in cytokines and their signaling pathways (such as tumor necrosis factor-alpha, interferon-gamma, SMAD proteins), mutations in genes encoding the RNA splicing machinery (SF3B1, SRSF2, ZRSR2, and U2AF1 genes), mutations in genes disrupting the epigenetic machinery (TET2, DNMT3A, DNMT3B, EZH2, ASXL1). In addition, abnormalities in regulatory T-cell dynamics and atypical interactions between the bone marrow microenvironment, stroma and progenitor cells, and abnormal maintenance of telomeres are also notable contributors to the complex pathogenesis of MDS. These pathways represent potential targets for novel therapies. Specific therapies include drugs targeting aberrant DNA methylation and chromatin remodeling, modulating/activating the immune system to enhance tumor-specific cellular immune responses and reduce anomalous cytokine signaling, and blocking abnormal interaction between hematopoietic progenitors and stromal cells.

Full Text

Duke Authors

Cited Authors

  • Zahid, MF; Patnaik, MM; Gangat, N; Hashmi, SK; Rizzieri, DA

Published Date

  • October 2016

Published In

Volume / Issue

  • 97 / 4

Start / End Page

  • 313 - 320

PubMed ID

  • 27147278

Pubmed Central ID

  • 27147278

Electronic International Standard Serial Number (EISSN)

  • 1600-0609

Digital Object Identifier (DOI)

  • 10.1111/ejh.12771


  • eng

Conference Location

  • England