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

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...

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Autores principales: Yi, Guoqiang, Wierenga, Albertus T.J., Petraglia, Francesca, Narang, Pankaj, Janssen-Megens, Eva M., Mandoli, Amit, Merkel, Angelika, Berentsen, Kim, Kim, Bowon, Matarese, Filomena, Singh, Abhishek A., Habibi, Ehsan, Prange, Koen H.M., Mulder, André B., Jansen, Joop H., Clarke, Laura, Heath, Simon, van der Reijden, Bert A., Flicek, Paul, Yaspo, Marie-Laure, Gut, Ivo, Bock, Christoph, Schuringa, Jan Jacob, Altucci, Lucia, Vellenga, Edo, Stunnenberg, Hendrik G., Martens, Joost H.A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363099/
https://www.ncbi.nlm.nih.gov/pubmed/30673601
http://dx.doi.org/10.1016/j.celrep.2018.12.098
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author Yi, Guoqiang
Wierenga, Albertus T.J.
Petraglia, Francesca
Narang, Pankaj
Janssen-Megens, Eva M.
Mandoli, Amit
Merkel, Angelika
Berentsen, Kim
Kim, Bowon
Matarese, Filomena
Singh, Abhishek A.
Habibi, Ehsan
Prange, Koen H.M.
Mulder, André B.
Jansen, Joop H.
Clarke, Laura
Heath, Simon
van der Reijden, Bert A.
Flicek, Paul
Yaspo, Marie-Laure
Gut, Ivo
Bock, Christoph
Schuringa, Jan Jacob
Altucci, Lucia
Vellenga, Edo
Stunnenberg, Hendrik G.
Martens, Joost H.A.
author_facet Yi, Guoqiang
Wierenga, Albertus T.J.
Petraglia, Francesca
Narang, Pankaj
Janssen-Megens, Eva M.
Mandoli, Amit
Merkel, Angelika
Berentsen, Kim
Kim, Bowon
Matarese, Filomena
Singh, Abhishek A.
Habibi, Ehsan
Prange, Koen H.M.
Mulder, André B.
Jansen, Joop H.
Clarke, Laura
Heath, Simon
van der Reijden, Bert A.
Flicek, Paul
Yaspo, Marie-Laure
Gut, Ivo
Bock, Christoph
Schuringa, Jan Jacob
Altucci, Lucia
Vellenga, Edo
Stunnenberg, Hendrik G.
Martens, Joost H.A.
author_sort Yi, Guoqiang
collection PubMed
description 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.
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spelling pubmed-63630992019-02-05 Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes Yi, Guoqiang Wierenga, Albertus T.J. Petraglia, Francesca Narang, Pankaj Janssen-Megens, Eva M. Mandoli, Amit Merkel, Angelika Berentsen, Kim Kim, Bowon Matarese, Filomena Singh, Abhishek A. Habibi, Ehsan Prange, Koen H.M. Mulder, André B. Jansen, Joop H. Clarke, Laura Heath, Simon van der Reijden, Bert A. Flicek, Paul Yaspo, Marie-Laure Gut, Ivo Bock, Christoph Schuringa, Jan Jacob Altucci, Lucia Vellenga, Edo Stunnenberg, Hendrik G. Martens, Joost H.A. Cell Rep Article 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. 2019-01-22 /pmc/articles/PMC6363099/ /pubmed/30673601 http://dx.doi.org/10.1016/j.celrep.2018.12.098 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Yi, Guoqiang
Wierenga, Albertus T.J.
Petraglia, Francesca
Narang, Pankaj
Janssen-Megens, Eva M.
Mandoli, Amit
Merkel, Angelika
Berentsen, Kim
Kim, Bowon
Matarese, Filomena
Singh, Abhishek A.
Habibi, Ehsan
Prange, Koen H.M.
Mulder, André B.
Jansen, Joop H.
Clarke, Laura
Heath, Simon
van der Reijden, Bert A.
Flicek, Paul
Yaspo, Marie-Laure
Gut, Ivo
Bock, Christoph
Schuringa, Jan Jacob
Altucci, Lucia
Vellenga, Edo
Stunnenberg, Hendrik G.
Martens, Joost H.A.
Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes
title Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes
title_full Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes
title_fullStr Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes
title_full_unstemmed Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes
title_short Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes
title_sort chromatin-based classification of genetically heterogeneous amls into two distinct subtypes with diverse stemness phenotypes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363099/
https://www.ncbi.nlm.nih.gov/pubmed/30673601
http://dx.doi.org/10.1016/j.celrep.2018.12.098
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