Unraveling the molecular pathophysiology of myelodysplastic syndromes Review uri icon

Overview

MeSH Major

  • Myelodysplastic Syndromes

abstract

  • Somatically acquired genetic abnormalities lead to the salient features that define myelodysplastic syndromes (MDS): clonal hematopoiesis, aberrant differentiation, peripheral cytopenias, and risk of progression to acute myeloid leukemia. Although specific karyotypic abnormalities have been linked to MDS for decades, more recent findings have demonstrated the importance of mutations within individual genes, focal alterations that are not apparent by standard cytogenetics, and aberrant epigenetic regulation of gene expression. The spectrum of genetic abnormalities in MDS implicates a wide range of molecular mechanisms in the pathogenesis of these disorders, including activation of tyrosine kinase signaling, genomic instability, impaired differentiation, altered ribosome function, and changes in the bone marrow microenvironment. Specific alterations present in individual patients with MDS may explain much of the heterogeneity in clinical phenotype associated with this disease and can predict prognosis and response to therapy. Elucidation of the full complement of genetic causes of MDS promises profound insight into the biology of the disease, improved classification and prognostic scoring schemes, and the potential for novel targeted therapies with molecular predictors of response.

publication date

  • February 10, 2011

Research

keywords

  • Review

Identity

Language

  • eng

PubMed Central ID

  • PMC3969457

Digital Object Identifier (DOI)

  • 10.1200/JCO.2010.31.1175

PubMed ID

  • 21220588

Additional Document Info

start page

  • 504

end page

  • 15

volume

  • 29

number

  • 5