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Subtype-specific regulatory network rewiring in acute myeloid leukemia

Lookup NU author(s): Dr Helen Blair, Professor Olaf Heidenreich

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by Nature Publishing Group, 2019.

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Abstract

© 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.


Publication metadata

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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