Subtype-specific regulatory network rewiring in acute myeloid leukemia.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
02
02
2018
accepted:
02
10
2018
pubmed:
14
11
2018
medline:
25
4
2019
entrez:
14
11
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30420649
doi: 10.1038/s41588-018-0270-1
pii: 10.1038/s41588-018-0270-1
pmc: PMC6330064
mid: EMS79897
doi:
Substances chimiques
NPM1 protein, human
0
Transcription Factors
0
Nucleophosmin
117896-08-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
151-162Subventions
Organisme : Medical Research Council
ID : MR/M009157/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P019609/1
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentIn
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