title: Epigenetic aberrations in myeloid malignancies (Review).
abstract: The development of novel technologies, such as massively parallel DNA sequencing, has led to the identification of several novel recurrent gene mutations, such as DNA methyltransferase (Dnmt)3a, ten-eleven-translocation oncogene family member 2 (TET2), isocitrate dehydrogenase (IDH)1/2, additional sex comb-like 1 (ASXL1), enhancer of zeste homolog 2 (EZH2) and ubiquitously transcribed tetratricopeptide repeat X chromosome (UTX) mutations in acute myeloid leukemia (AML) and other myeloid malignancies. These findings strongly suggest a link between recurrent genetic alterations and aberrant epigenetic regulations, resulting from an abnormal DNA methylation and histone modification status. This review focuses on the current findings of aberrant epigenetic signatures by these newly described genetic alterations. Moreover, epigenetic aberrations resulting from transcription factor aberrations, such as mixed lineage leukemia (MLL) rearrangement, ecotropic viral integration site 1 (Evi1) overexpression, chromosomal translocations and the downregulation of PU.1 are also described.
authors.affiliation: Division of Hematology, Kitasato University School of Allied Health Sciences; Division of Molecular Hematology, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa 252-0373, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D000090205:DNA Methyltransferase 3A; D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D015870:Gene Expression; D015973:Gene Expression Regulation, Leukemic; D056466:Histone Demethylases / Q000235:genetics; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D007951:Leukemia, Myeloid / Q000235:genetics*; D000074008:MDS1 and EVI1 Complex Locus Protein; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D063151:Polycomb Repressive Complex 2 / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011519:Proto-Oncogenes / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: C473949:ASXL1 protein, human; D004268:DNA-Binding Proteins; C000717967:DNMT3A protein, human; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D049308:Dioxygenases; C541081:TET2 protein, human; D056466:Histone Demethylases; C523998:KDM6A protein, human; D000090205:DNA Methyltransferase 3A; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2