title: A key role for EZH2 and associated genes in mouse and human adult T-cell acute leukemia.
abstract: In this study, we show the high frequency of spontaneous γδ T-cell leukemia (T-ALL) occurrence in mice with biallelic deletion of enhancer of zeste homolog 2 (Ezh2). Tumor cells show little residual H3K27 trimethylation marks compared with controls. EZH2 is a component of the PRC2 Polycomb group protein complex, which is associated with DNA methyltransferases. Using next-generation sequencing, we identify alteration in gene expression levels of EZH2 and acquired mutations in PRC2-associated genes (DNMT3A and JARID2) in human adult T-ALL. Together, these studies document that deregulation of EZH2 and associated genes leads to the development of mouse, and likely human, T-ALL.
authors.affiliation: The Leucegene Group, Institute for Research in Immunology and Cancer, University of Montreal, Montreal, Quebec H3T 1J4, Canada.
authors.forename: Camille
authors.initials: C
authors.lastname: Simon
authors.forename: Jalila
authors.initials: J
authors.lastname: Chagraoui
authors.forename: Jana
authors.initials: J
authors.lastname: Krosl
authors.forename: Patrick
authors.initials: P
authors.lastname: Gendron
authors.forename: Brian
authors.initials: B
authors.lastname: Wilhelm
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lemieux
authors.forename: Geneviève
authors.initials: G
authors.lastname: Boucher
authors.forename: Pierre
authors.initials: P
authors.lastname: Chagnon
authors.forename: Simon
authors.initials: S
authors.lastname: Drouin
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Lambert
authors.forename: Claude
authors.initials: C
authors.lastname: Rondeau
authors.forename: Annie
authors.initials: A
authors.lastname: Bilodeau
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lavallée
authors.forename: Martin
authors.initials: M
authors.lastname: Sauvageau
authors.forename: Josée
authors.initials: J
authors.lastname: Hébert
authors.forename: Guy
authors.initials: G
authors.lastname: Sauvageau
mesh_terms: D000208:Acute Disease; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2