Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes.

Chromatin / genetics Core Binding Factor Alpha 2 Subunit / genetics Humans Leukemia, Myeloid, Acute / classification Mutation Nuclear Proteins / genetics Nucleophosmin Oncogene Proteins, Fusion / genetics
AML DNA accessibility acute myeloid leukemia chromatin states epigenome histone marks stemness transcriptome

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
22 01 2019
Historique:
received: 27 06 2018
revised: 27 09 2018
accepted: 21 12 2018
entrez: 24 1 2019
pubmed: 24 1 2019
medline: 7 3 2020
Statut: ppublish

Résumé

Global investigation of histone marks in acute myeloid leukemia (AML) remains limited. Analyses of 38 AML samples through integrated transcriptional and chromatin mark analysis exposes 2 major subtypes. One subtype is dominated by patients with NPM1 mutations or MLL-fusion genes, shows activation of the regulatory pathways involving HOX-family genes as targets, and displays high self-renewal capacity and stemness. The second subtype is enriched for RUNX1 or spliceosome mutations, suggesting potential interplay between the 2 aberrations, and mainly depends on IRF family regulators. Cellular consequences in prognosis predict a relatively worse outcome for the first subtype. Our integrated profiling establishes a rich resource to probe AML subtypes on the basis of expression and chromatin data.

Identifiants

DOI: 10.1016/j.celrep.2018.12.098 PMID: 30673601 PMC: PMC6363099
pubmed: 30673601
pii: S2211-1247(18)32058-8
doi: 10.1016/j.celrep.2018.12.098
pmc: PMC6363099
mid: EMS81493
pii:
doi:

Substances chimiques

Chromatin 0
Core Binding Factor Alpha 2 Subunit 0
NPM1 protein, human 0
Nuclear Proteins 0
Oncogene Proteins, Fusion 0
RUNX1 protein, human 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

1059-1069.e6

Subventions

Organisme : Wellcome Trust
ID : 108749
Pays : United Kingdom

Informations de copyright

Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Guoqiang Yi (G)

Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands.

Albertus T J Wierenga (ATJ)

Department of Hematology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands; Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.

Francesca Petraglia (F)

Dipartimento di Biochimica, Biofisica e Patologia generale, Università degli Studi della Campania "Luigi Vanvitelli," Vico L. De Crecchio 7, 80138 Napoli, Italy.

Pankaj Narang (P)

Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands.

Eva M Janssen-Megens (EM)

Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands.

Amit Mandoli (A)

Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands.

Angelika Merkel (A)

Centro Nacional de Análisis Genómico (CNAG), Parc Científic de Barcelona, Barcelona, Spain.

Kim Berentsen (K)

Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands.

Bowon Kim (B)

Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands.

Filomena Matarese (F)

Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands.

Abhishek A Singh (AA)

Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands.

Ehsan Habibi (E)

Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands.

Koen H M Prange (KHM)

Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands.

André B Mulder (AB)

Department of Hematology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.

Joop H Jansen (JH)

Department of Laboratory Medicine, Laboratory of Hematology, Radboud University, 6525 GA Nijmegen, the Netherlands.

Laura Clarke (L)

European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.

Simon Heath (S)

Centro Nacional de Análisis Genómico (CNAG), Parc Científic de Barcelona, Barcelona, Spain.

Bert A van der Reijden (BA)

Department of Laboratory Medicine, Laboratory of Hematology, Radboud University, 6525 GA Nijmegen, the Netherlands.

Paul Flicek (P)

European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.

Marie-Laure Yaspo (ML)

Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.

Ivo Gut (I)

Centro Nacional de Análisis Genómico (CNAG), Parc Científic de Barcelona, Barcelona, Spain.

Christoph Bock (C)

CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, 1090 Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria; Max Planck Institute for Informatics, Saarland Informatics Campus, 66123 Saarbrücken, Germany.

Jan Jacob Schuringa (JJ)

Department of Hematology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.

Lucia Altucci (L)

Dipartimento di Biochimica, Biofisica e Patologia generale, Università degli Studi della Campania "Luigi Vanvitelli," Vico L. De Crecchio 7, 80138 Napoli, Italy.

Edo Vellenga (E)

Department of Hematology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.

Hendrik G Stunnenberg (HG)

Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands.

Joost H A Martens (JHA)

Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands. Electronic address: j.martens@ncmls.ru.nl.

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Structures de chromosome › Chromatine › Chromatin-Based Classification of Genetically...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription CBF › Sous-unités alpha du facteur CBF › Sous-unité alpha 2 du facteur CBF › Chromatin-Based Classification of Genetically...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Chromatin-Based Classification of Genetically...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Leucémies › Leucémie myéloïde › Leucémie aigüe myéloïde › Chromatin-Based Classification of Genetically...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Chromatin-Based Classification of Genetically...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Chromatin-Based Classification of Genetically...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Nucléophosmine › Chromatin-Based Classification of Genetically...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines de fusion oncogènes › Chromatin-Based Classification of Genetically...