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

Autor:	Yi G; Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands., 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., Petraglia F; Dipartimento di Biochimica, Biofisica e Patologia generale, Università degli Studi della Campania 'Luigi Vanvitelli,' Vico L. De Crecchio 7, 80138 Napoli, Italy., Narang P; Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands., Janssen-Megens EM; Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands., Mandoli A; Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands., Merkel A; Centro Nacional de Análisis Genómico (CNAG), Parc Científic de Barcelona, Barcelona, Spain., Berentsen K; Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands., Kim B; Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands., Matarese F; Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands., Singh AA; Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands., Habibi E; Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands., Prange KHM; Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands., Mulder AB; Department of Hematology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands., Jansen JH; Department of Laboratory Medicine, Laboratory of Hematology, Radboud University, 6525 GA Nijmegen, the Netherlands., Clarke L; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK., Heath S; Centro Nacional de Análisis Genómico (CNAG), Parc Científic de Barcelona, Barcelona, Spain., van der Reijden BA; Department of Laboratory Medicine, Laboratory of Hematology, Radboud University, 6525 GA Nijmegen, the Netherlands., Flicek P; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK., Yaspo ML; Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany., Gut I; Centro Nacional de Análisis Genómico (CNAG), Parc Científic de Barcelona, Barcelona, Spain., 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., Schuringa JJ; Department of Hematology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands., Altucci L; Dipartimento di Biochimica, Biofisica e Patologia generale, Università degli Studi della Campania 'Luigi Vanvitelli,' Vico L. De Crecchio 7, 80138 Napoli, Italy., Vellenga E; Department of Hematology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands., Stunnenberg HG; Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands., Martens JHA; Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands. Electronic address: j.martens@ncmls.ru.nl.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2019 Jan 22; Vol. 26 (4), pp. 1059-1069.e6.
DOI:	10.1016/j.celrep.2018.12.098
Abstrakt:	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. (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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