Epigenetic changes in the myelodysplastic syndrome.
Epigenetic mechanisms, such as DNA methylation and histone modifications, drive stable, clonally propagated changes in gene expression and can therefore serve as molecular mediators of pathway dysfunction in neoplasia. Myelodysplastic syndrome (MDS) is characterized by frequent epigenetic abnormalities, including the hypermethylation of genes that control proliferation, adhesion, and other characteristic features of this leukemia. Aberrant DNA hypermethylation is associated with a poor prognosis in MDS that can be accounted for by more rapid progression to acute myeloid leukemia. In turn, treatment with drugs that modify epigenetic pathways (DNA methylation and histone deacetylation inhibitors) induces durable remissions and prolongs life in MDS, offering some hope and direction in the future management of this deadly disease.
Issa
Jean-Pierre
JP
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA. jpissa@mdanderson.org
D000107:Acetylation / Q000187:drug effects; D000208:Acute Disease; D001374:Azacitidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D044127:Epigenesis, Genetic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000502:physiology; D006657:Histones / Q000378:metabolism; D006801:Humans; D007951:Leukemia, Myeloid / Q000209:etiology / Q000517:prevention & control; D008745:Methylation; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects
D056572:Histone Deacetylase Inhibitors; D006657:Histones; D000077209:Decitabine; D006655:Histone Deacetylases; D001374:Azacitidine