The genetic basis of phenotypic heterogeneity in myelodysplastic syndromes

Nat Rev Cancer. 2012 Dec;12(12):849-59. doi: 10.1038/nrc3321.


Myelodysplastic syndromes (MDS) are malignant clonal disorders of haematopoietic stem cells and their microenvironment, affecting older individuals (median age ∼70 years). Unique features that are associated with MDS - but which are not necessarily present in every patient with MDS - include excessive apoptosis in maturing clonal cells, a pro-inflammatory bone marrow microenvironment, specific chromosomal abnormalities, abnormal ribosomal protein biogenesis, the presence of uniparental disomy, and mutations affecting genes involved in proliferation, methylation and epigenetic modifications. Although emerging insights establish an association between molecular abnormalities and the phenotypic heterogeneity of MDS, their origin and progression remain enigmatic.

Publication types

  • Review

MeSH terms

  • Apoptosis / genetics
  • Chromatin / genetics
  • Chromosome Aberrations
  • Epigenesis, Genetic
  • Gene Expression Profiling
  • Genes, Tumor Suppressor
  • Humans
  • MicroRNAs
  • Mutation*
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / pathology*
  • Oncogenes
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Spliceosomes / genetics
  • Uniparental Disomy / genetics
  • Uniparental Disomy / pathology


  • Chromatin
  • MicroRNAs