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Crit Rev Oncol Hematol. 2013 Nov;88(2):231-45. doi: 10.1016/j.critrevonc.2013.06.004. Epub 2013 Jul 7.

Epigenetics in focus: pathogenesis of myelodysplastic syndromes and the role of hypomethylating agents.

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1
Haematology unit, University of Florence, Florence, Italy. Electronic address: valeria.santini@unifi.it.

Abstract

Dysregulation of cellular epigenetic machinery is considered a major pathogenetic determinant in many malignancies, including myelodysplastic syndromes (MDS). The importance of epigenetic dysfunction in MDS is reflected by the success of hypomethylating agents as standard of care for their treatment. Although these agents improve both survival and quality of life, knowledge gaps remain regarding the precise role of epigenetics in the pathogenesis of MDS and mechanisms by which hypomethylating agents exert their clinical effects. This article reviews the pathogenic role of epigenetic alterations in MDS, including the relationship between genetic and epigenetic abnormalities, and highlights emerging evidence that hypomethylating agents may reprogram the "methylome" while re-establishing hematopoiesis.

KEYWORDS:

Acute myeloid leukemia; DNA hypermethylation; Epigenetics; Hypomethylating agents; Myelodysplastic syndromes

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