title: Epigenetics in focus: pathogenesis of myelodysplastic syndromes and the role of hypomethylating agents.
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.
authors.affiliation: Haematology unit, University of Florence, Florence, Italy. Electronic address: valeria.santini@unifi.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Santini
authors.forename: Ari
authors.initials: A
authors.lastname: Melnick
authors.forename: Jaroslaw P
authors.initials: JP
authors.lastname: Maciejewski
authors.forename: Estelle
authors.initials: E
authors.lastname: Duprez
authors.forename: Clara
authors.initials: C
authors.lastname: Nervi
authors.forename: Lucio
authors.initials: L
authors.lastname: Cocco
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Ford
authors.forename: Ghulam
authors.initials: G
authors.lastname: Mufti
mesh_terms: D002869:Chromosome Aberrations; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D057890:Epigenomics; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006657:Histones / Q000378:metabolism; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics; D008745:Methylation; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000235:genetics*
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones
keywords: Acute myeloid leukemia; DNA hypermethylation; Epigenetics; Hypomethylating agents; Myelodysplastic syndromes