Chronic FLT3-ITD Signaling in Acute Myeloid Leukemia Is Connected to a Specific Chromatin Signature

Pierre Cauchy, Sally R. James, Joaquin Zacarias Cabeza, Anetta Ptasinska, Maria Imperato, Salam A. Assi, Jason Piper, Martina Canestraro, Maarten Hoogenkamp, Manoj Raghavan, Justin Loke, Susanna Akiki, Samuel J. Clokie, Stephen J. Richards, David R. Westhead, Michael Griffiths, Sascha Ott, Constanze Bonifer*, Peter Cockerill

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)
193 Downloads (Pure)


Acute myeloid leukemia (AML) is characterized by recurrent mutations that affect the epigenetic regulatory machinery and signaling molecules, leading to a block in hematopoietic differentiation. Constitutive signaling from mutated growth factor receptors is a major driver of leukemic growth, but how aberrant signaling affects the epigenome in AML is less understood. Furthermore, AML cells undergo extensive clonal evolution, and the mutations in signaling genes are often secondary events. To elucidate how chronic growth factor signaling alters the transcriptional network in AML, we performed a system-wide multi-omics study of primary cells from patients suffering from AML with internal tandem duplications in the FLT3 transmembrane domain (FLT3-ITD). This strategy revealed cooperation between the MAP kinase (MAPK) inducible transcription factor AP-1 and RUNX1 as a major driver of a common, FLT3-ITD-specific gene expression and chromatin signature, demonstrating a major impact of MAPK signaling pathways in shaping the epigenome of FLT3-ITD AML.

Original languageEnglish
Pages (from-to)821-836
Number of pages16
JournalCell Reports
Issue number5
Early online date23 Jul 2015
Publication statusPublished - 4 Aug 2015

Bibliographical note

Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.


  • acute myeloid leukaemia

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)


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