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Molecular Genetics of Myelodysplastic Syndromes

  1. Rafael Bejar1,
  2. David P Steensma2

Published Online: 15 NOV 2012

DOI: 10.1002/9780470015902.a0023872



How to Cite

Bejar, R. and Steensma, D. P. 2012. Molecular Genetics of Myelodysplastic Syndromes. eLS. .

Author Information

  1. 1

    University of California, San Diego, La Jolla, California, USA

  2. 2

    Dana-Farber Cancer Institute, Boston, Massachusetts, USA

Publication History

  1. Published Online: 15 NOV 2012


Myelodysplastic syndromes (MDS) are a group of clonal haematopoietic disorders characterised clinically by inefficient haematopoiesis, cytopenias of the peripheral blood and a risk of progression to acute myeloid leukaemia (AML). Molecularly, MDS can be associated with a wide range of acquired chromosomal abnormalities, epigenetic alterations and single gene mutations. These abnormalities affect diverse molecular pathways including ribonucleic acid (RNA) splicing machinery, epigenetic modifiers, haematopoietic transcription factors, receptor tyrosine kinase signalling, cell cycle regulation and apoptosis. The particular combination of somatic genetic lesions in any given patient will influence how their disease is manifested, and together with individual background germline genotype may explain much of the clinical heterogeneity associated with MDS. Here, the common genetic abnormalities that underlie MDS and how these abnormalities influence the development and progression of these disorders have been reviewed.

Key Concepts:

  • MDS represent a collection of disorders marked by abnormal, inefficient haematopoiesis, cytopenias of the peripheral blood and a predisposition for progression to AML.

  • Like other haematopoietic malignancies, MDS arise from the clonal expansion of a single, abnormal haematopoietic cell.

  • The abnormal MDS cells that maintain the disease have the ability to self-renew and clonally expand because they have a selective growth advantage compared to their normal counterparts.

  • Impaired haematopoietic differentiation in MDS can lead to cytopenias or to the production of terminally differentiated cells with abnormal function.

  • A combination of somatic genetic abnormalities (acquired changes to the deoxyribonucleic acid (DNA) coding sequence), epigenetic abnormalities (heritable changes in gene expression) and marrow microenvironmental abnormalities contribute to the development and progression of MDS.

  • Approximately, 50% of MDS cells have a chromosomal abnormality detectable by routine metaphase karyotype analysis.

  • More than 75% of patients have acquired mutations in one or more genes known to be recurrently altered in MDS.

  • Recurrent mutations in MDS implicate several molecular pathways in the development and progression of disease including; altered RNA splicing mechanisms, epigenetic changes in DNA methylation and histone modifications, activation of growth factor signalling cascades, impaired differentiation and abnormal regulation of cell cycle and apoptosis.

  • Acquired mutations in several MDS genes have prognostic significance that is independent of clinically based prognostic scoring systems.

  • Chromosomal abnormalities and mutations in some genes can predict response to specific therapies used to treat patients with MDS.


  • myelodysplastic syndromes;
  • somatic mutations;
  • refractory anaemia;
  • thrombocytopenia;
  • splicing factors;
  • epigenetics;
  • ring sideroblasts;
  • cytogenetic abnormalities;
  • acute myeloid leukaemia;
  • stem cell transplantation;
  • hypomethylating agents;
  • azacitidine;
  • decitabine;
  • lenalidomide