title: Developmental-stage-dependent transcriptional response to leukaemic oncogene expression.
abstract: Acute myeloid leukaemia (AML) is characterized by a block in myeloid differentiation the stage of which is dependent on the nature of the transforming oncogene and the developmental stage of the oncogenic hit. This is also true for the t(8;21) translocation that gives rise to the RUNX1-ETO fusion protein and initiates the most common form of human AML. Here we study the differentiation of mouse embryonic stem cells expressing an inducible RUNX1-ETO gene into blood cells as a model, combined with genome-wide analyses of transcription factor binding and gene expression. RUNX1-ETO interferes with both the activating and repressive function of its normal counterpart, RUNX1, at early and late stages of blood cell development. However, the response of the transcriptional network to RUNX1-ETO expression is developmental stage specific, highlighting the molecular mechanisms determining specific target cell expansion after an oncogenic hit.
authors.affiliation: School of Cancer Sciences, Institute for Biomedical Research, University of Birmingham at Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Kakkad
authors.initials: K
authors.lastname: Regha
authors.affiliation: School of Cancer Sciences, Institute for Biomedical Research, University of Birmingham at Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Salam A
authors.initials: SA
authors.lastname: Assi
authors.affiliation: CRUK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors.forename: Olga
authors.initials: O
authors.lastname: Tsoulaki
authors.affiliation: School of Cancer Sciences, Institute for Biomedical Research, University of Birmingham at Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Gilmour
authors.affiliation: CRUK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors.forename: Georges
authors.initials: G
authors.lastname: Lacaud
authors.affiliation: School of Cancer Sciences, Institute for Biomedical Research, University of Birmingham at Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Constanze
authors.initials: C
authors.lastname: Bonifer
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D047369:Chromatin Immunoprecipitation; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018274:Electroporation; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D053263:Gene Regulatory Networks; D006410:Hematopoiesis / Q000235:genetics*; D066298:In Vitro Techniques; D015470:Leukemia, Myeloid, Acute; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*; D059467:Transcriptome; D014178:Translocation, Genetic
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; C493598:MTG8 protein, mouse; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C493726:Runx1 protein, mouse; D014157:Transcription Factors