Myelodysplastic syndromes: molecular pathogenesis and genomic changes

Ann Hematol. 2008 Oct;87(10):777-95. doi: 10.1007/s00277-008-0502-z. Epub 2008 May 31.


Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis presenting with peripheral cytopenias in combination with a hyperplastic bone marrow and an increased risk of evolution to acute myeloid leukemia. The classification systems such as the WHO classification mainly rely on morphological criteria and are supplemented by the International Prognostic Scoring System which takes cytogenetical changes into consideration when determining the prognosis of MDS but wide intra-subtype variations do exist. The pathomechanisms causing primary MDS require further work. Development and progression of MDS is suggested to be a multistep alteration to hematopoietic stem cells. Different molecular alterations have been described, affecting genes involved in cell-cycle control, mitotic checkpoints, and growth factor receptors. Secondary signal proteins and transcription factors, which gives the cell a growth advantage over its normal counterpart, may be affected as well. The accumulation of such defects may finally cause the leukemic transformation of MDS.

Publication types

  • Review

MeSH terms

  • Bone Marrow Cells / physiology
  • Cell Cycle / physiology
  • Chromosome Aberrations
  • DNA, Mitochondrial / genetics
  • Epigenesis, Genetic
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Myelodysplastic Syndromes / classification
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / pathology
  • Myelodysplastic Syndromes / physiopathology*
  • Neovascularization, Pathologic
  • Polymorphism, Single Nucleotide
  • Signal Transduction / physiology
  • Transcription Factors / metabolism


  • DNA, Mitochondrial
  • Transcription Factors