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Abstract
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 language | English |
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Pages (from-to) | 821-836 |
Number of pages | 16 |
Journal | Cell Reports |
Volume | 12 |
Issue number | 5 |
Early online date | 23 Jul 2015 |
DOIs | |
Publication status | Published - 4 Aug 2015 |
Bibliographical note
Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.Keywords
- acute myeloid leukaemia
ASJC Scopus subject areas
- General Medicine
- General Immunology and Microbiology
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Dive into the research topics of 'Chronic FLT3-ITD Signaling in Acute Myeloid Leukemia Is Connected to a Specific Chromatin Signature'. Together they form a unique fingerprint.Projects
- 1 Finished
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Mechanistic Insights into the Interplay Between Transcription Factors and the Epigenetic Regulatory Machinery in Normal and Leukaemic Cells
Bonifer, C. (Principal Investigator) & Cockerill, P. (Co-Investigator)
1/07/12 → 31/03/17
Project: Research