Developmental-stage-dependent transcriptional response to leukaemic oncogene expression

Research output: Contribution to journalArticle

Authors

  • Kakkad Regha
  • Olga Tsoulaki
  • Georges Lacaud

Colleges, School and Institutes

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.

Details

Original languageEnglish
Article number7203
JournalNature Communications
Volume6
Publication statusPublished - 28 May 2015

Keywords

  • transcriptional response, oncogene expression