TitleEpigenetics in focus: pathogenesis of myelodysplastic syndromes and the role of hypomethylating agents.
Publication TypeJournal Article
Year of Publication2013
AuthorsSantini, Valeria, Melnick Ari, Maciejewski Jaroslaw P., Duprez Estelle, Nervi Clara, Cocco Lucio, Ford Kevin G., and Mufti Ghulam
JournalCrit Rev Oncol Hematol
Volume88
Issue2
Pagination231-45
Date Published2013 Nov
ISSN1879-0461
KeywordsChromosome Aberrations, DNA Methylation, Epigenesis, Genetic, Epigenomics, Histone Deacetylase Inhibitors, Histones, Humans, Leukemia, Myeloid, Methylation, Myelodysplastic Syndromes
Abstract

<p>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.</p>

DOI10.1016/j.critrevonc.2013.06.004
Alternate JournalCrit Rev Oncol Hematol
PubMed ID23838480
Grant ListMR/J006742/1 / MRC_ / Medical Research Council / United Kingdom
/ BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom