title: Integrating genetics and epigenetics in myelodysplastic syndromes: advances in pathogenesis and disease evolution.
abstract: The myelodysplastic syndromes (MDS) are a group of clonal diseases characterized by inefficient haematopoiesis, increased apoptosis and risk of evolution to acute myeloid leukaemia. Alterations in epigenetic processes, including DNA methylation, histone modifications, miRNA and splicing machinery, are well known pathogenical events in MDS. Although many advances have been made in determining the mutational frequency, distribution and association affecting these epigenomic regulators, functional integration to better understand pathogenesis of the disease is a challenging and expanding area. Recent studies are shedding light on the molecular basis of myelodysplasia and how mutations and epimutations can induce and promote this neoplastic process through aberrant transcription factor function (RUNX1, ETV6, TP53), kinase signalling (FLT3, NRAS, KIT, CBL) and epigenetic deregulation (TET2, IDH1/2, DNMT3A, EZH2, ASXL1, SF3B1, U2AF1, SRSF2, ZRSR2). In this review we will try to focus on the description of these mutations, their impact on prognosis, the functional connections between the different epigenetic pathways, and the existing and future therapies targeting these processes.
authors.affiliation: Department of Hematology, Universitary Hospital of La Paz, Madrid, Spain.
authors.forename: Guillermo Montalbán
authors.initials: GM
authors.lastname: Bravo
authors.forename: Elinor
authors.initials: E
authors.lastname: Lee
authors.forename: Bryan
authors.initials: B
authors.lastname: Merchan
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Guillermo
authors.initials: G
authors.lastname: García-Manero
mesh_terms: D000818:Animals; D044127:Epigenesis, Genetic; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D011379:Prognosis
keywords: epigenetics; genetics; myelodysplastic syndromes