Subtype-specific regulatory network rewiring in acute myeloid leukemia

Salam A. Assi, Maria Rosaria Imperato, Daniel J. L. Coleman, Anna Pickin, Sandeep Potluri, Anetta Ptasinska, Paulynn Suyin Chin, Helen Blair, Pierre Cauchy, Sally R. James, Joaquin Zacarias-cabeza, L. Niall Gilding, Andrew Beggs, Sam Clokie, Justin C. Loke, Phil Jenkin, Ash Uddin, Ruud Delwel, Stephen J. Richards, Manoj RaghavanMichael J. Griffiths, Olaf Heidenreich, Peter N. Cockerill, Constanze Bonifer

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)
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Abstract

Acute myeloid leukemia (AML) is a heterogeneous disease caused by a variety of mutations 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 focussed on specific sub-groups of patients carrying mutations in genes encoding transcription factors (RUNX1, CEBPα) and signaling molecules (FTL3-ITD, RAS, NPM1). Integrated analysis of these data demonstrates that each mutant regulator establishes a specific transcriptional and signaling network unrelated to normal cells sustaining the expression of unique sets of genes required for AML growth and maintenance.
Original languageEnglish
Pages (from-to)151-162
Number of pages12
JournalNature Genetics
Volume51
Issue number1
Early online date12 Nov 2018
DOIs
Publication statusPublished - Jan 2019

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