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Developmental-stage-dependent transcriptional response to leukaemic oncogene expression

Author

Listed:
  • 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)

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.

Suggested Citation

  • Kakkad Regha & Salam A. Assi & Olga Tsoulaki & Jane Gilmour & Georges Lacaud & Constanze Bonifer, 2015. "Developmental-stage-dependent transcriptional response to leukaemic oncogene expression," Nature Communications, Nature, vol. 6(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8203
    DOI: 10.1038/ncomms8203
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    Cited by:

    1. Sophie G. Kellaway & Sandeep Potluri & Peter Keane & Helen J. Blair & Luke Ames & Alice Worker & Paulynn S. Chin & Anetta Ptasinska & Polina K. Derevyanko & Assunta Adamo & Daniel J. L. Coleman & Naee, 2024. "Leukemic stem cells activate lineage inappropriate signalling pathways to promote their growth," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

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