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Integrating genetics and epigenetics in myelodysplastic syndromes: advances in pathogenesis and disease evolution
Author(s) -
Bravo Guillermo Montalbán,
Lee Elinor,
Merchan Bryan,
Kantarjian Hagop M.,
GarcíaManero Guillermo
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12957
Subject(s) - epigenetics , epigenomics , biology , myelodysplastic syndromes , dna methylation , runx1 , genetics , cancer research , genome instability , neuroblastoma ras viral oncogene homolog , transcription factor , bioinformatics , mutation , immunology , gene , gene expression , dna damage , dna , bone marrow , kras
Summary 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, mi RNA 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 ( RUNX 1 , ETV 6 , TP 53 ), kinase signalling ( FLT 3 , NRAS , KIT , CBL ) and epigenetic deregulation ( TET 2 , IDH 1/2 , DNMT 3A , EZH 2 , ASXL 1 , SF 3B1 , U2 AF 1 , SRSF 2 , ZRSR 2 ). 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.