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Lookup NU author(s): Dr Helen Blair, Professor Olaf Heidenreich
This is the authors' accepted manuscript of an article that has been published in its final definitive form by Nature Publishing Group, 2019.
For re-use rights please refer to the publisher's terms and conditions.
© 2018, The Author(s), under exclusive licence to Springer Nature America, Inc. Acute myeloid leukemia (AML) is a heterogeneous disease caused by a variety of alterations in transcription factors, epigenetic regulators and signaling molecules. To determine how different mutant regulators establish AML subtype–specific transcriptional networks, we performed a comprehensive global analysis of cis-regulatory element activity and interaction, transcription factor occupancy and gene expression patterns in purified leukemic blast cells. Here, we focused on specific subgroups of subjects carrying mutations in genes encoding transcription factors (RUNX1, CEBPα), signaling molecules (FTL3-ITD, RAS) and the nuclear protein NPM1). Integrated analysis of these data demonstrates that each mutant regulator establishes a specific transcriptional and signaling network unrelated to that seen in normal cells, sustaining the expression of unique sets of genes required for AML growth and maintenance.
Author(s): Assi SA, Imperato MR, Coleman DJL, Pickin A, Potluri S, Ptasinska A, Chin PS, Blair H, Cauchy P, James SR, Zacarias-Cabeza J, Gilding LN, Beggs A, Clokie S, Loke JC, Jenkin P, Uddin A, Delwel R, Richards SJ, Raghavan M, Griffiths MJ, Heidenreich O, Cockerill PN, Bonifer C
Publication type: Article
Publication status: Published
Journal: Nature Genetics
Year: 2019
Volume: 51
Issue: 1
Pages: 151-162
Print publication date: 01/01/2019
Online publication date: 12/11/2018
Acceptance date: 02/10/2018
Date deposited: 18/02/2020
ISSN (print): 1061-4036
ISSN (electronic): 1546-1718
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/s41588-018-0270-1
DOI: 10.1038/s41588-018-0270-1
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