Developmental-stage-dependent transcriptional response to leukaemic oncogene expression

Kakkad Regha, Salam A. Assi, Olga Tsoulaki, Jane Gilmour, Georges Lacaud and Constanze Bonifer ()
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Kakkad Regha: School of Cancer Sciences, Institute for Biomedical Research, University of Birmingham at Edgbaston
Salam A. Assi: School of Cancer Sciences, Institute for Biomedical Research, University of Birmingham at Edgbaston
Olga Tsoulaki: CRUK Manchester Institute, The University of Manchester
Jane Gilmour: School of Cancer Sciences, Institute for Biomedical Research, University of Birmingham at Edgbaston
Georges Lacaud: CRUK Manchester Institute, The University of Manchester
Constanze Bonifer: School of Cancer Sciences, Institute for Biomedical Research, University of Birmingham at Edgbaston

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8203

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