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

Guoqiang Yi; Albertus T.J. Wierenga; Francesca Petraglia; Pankaj Narang; Eva M. Janssen-Megens; Amit Mandoli; Angelika Merkel; Kim Berentsen; Bowon Kim; Filomena Matarese; Abhishek A. Singh; Ehsan Habibi; Koen H.M. Prange; André B. Mulder; Joop H. Jansen; Laura Clarke; Simon Heath; Bert A. van der Reijden; Paul Flicek; Marie Laure Yaspo; Ivo Gut; Christoph Bock; Jan Jacob Schuringa; Lucia Altucci; Edo Vellenga; Hendrik G. Stunnenberg; Joost H.A. Martens

doi:10.1016/j.celrep.2018.12.098

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

Guoqiang Yi, Albertus T.J. Wierenga, Francesca Petraglia, Pankaj Narang, Eva M. Janssen-Megens, Amit Mandoli, Angelika Merkel, Kim Berentsen, Bowon Kim, Filomena Matarese, Abhishek A. Singh, Ehsan Habibi, Koen H.M. Prange, André B. Mulder, Joop H. Jansen, Laura Clarke, Simon Heath, Bert A. van der Reijden, Paul Flicek, Marie Laure YaspoIvo Gut, Christoph Bock, Jan Jacob Schuringa, Lucia Altucci, Edo Vellenga, Hendrik G. Stunnenberg, Joost H.A. Martens

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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.

Originele taal-2	Engels
Pagina's (van-tot)	1059-1069.e6
Tijdschrift	Cell Reports
Volume	26
Nummer van het tijdschrift	4
DOI's	https://doi.org/10.1016/j.celrep.2018.12.098
Status	Gepubliceerd - 22 jan. 2019
Extern gepubliceerd	Ja

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10.1016/j.celrep.2018.12.098

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Yi, G., Wierenga, A. T. J., Petraglia, F., Narang, P., Janssen-Megens, E. M., Mandoli, A., Merkel, A., Berentsen, K., Kim, B., Matarese, F., Singh, A. A., Habibi, E., Prange, K. H. M., Mulder, A. B., Jansen, J. H., Clarke, L., Heath, S., van der Reijden, B. A., Flicek, P., ... Martens, J. H. A. (2019). Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes. Cell Reports, 26(4), 1059-1069.e6. https://doi.org/10.1016/j.celrep.2018.12.098

@article{061dd1322ab64103972cb40c31c78553,

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

abstract = "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.",

keywords = "acute myeloid leukemia, AML, chromatin states, DNA accessibility, epigenome, histone marks, stemness, transcriptome",

author = "Guoqiang Yi and Wierenga, {Albertus T.J.} and Francesca Petraglia and Pankaj Narang and Janssen-Megens, {Eva M.} and Amit Mandoli and Angelika Merkel and Kim Berentsen and Bowon Kim and Filomena Matarese and Singh, {Abhishek A.} and Ehsan Habibi and Prange, {Koen H.M.} and Mulder, {Andr{\'e} B.} and Jansen, {Joop H.} and Laura Clarke and Simon Heath and {van der Reijden}, {Bert A.} and Paul Flicek and Yaspo, {Marie Laure} and Ivo Gut and Christoph Bock and Schuringa, {Jan Jacob} and Lucia Altucci and Edo Vellenga and Stunnenberg, {Hendrik G.} and Martens, {Joost H.A.}",

note = "Publisher Copyright: {\textcopyright} 2018 The Authors",

year = "2019",

month = jan,

day = "22",

doi = "10.1016/j.celrep.2018.12.098",

language = "English",

volume = "26",

pages = "1059--1069.e6",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "4",

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Yi, G, Wierenga, ATJ, Petraglia, F, Narang, P, Janssen-Megens, EM, Mandoli, A, Merkel, A, Berentsen, K, Kim, B, Matarese, F, Singh, AA, Habibi, E, Prange, KHM, Mulder, AB, Jansen, JH, Clarke, L, Heath, S, van der Reijden, BA, Flicek, P, Yaspo, ML, Gut, I, Bock, C, Schuringa, JJ, Altucci, L, Vellenga, E, Stunnenberg, HG & Martens, JHA 2019, 'Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes', Cell Reports, vol. 26, nr. 4, blz. 1059-1069.e6. https://doi.org/10.1016/j.celrep.2018.12.098

TY - JOUR

T1 - Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes

AU - Yi, Guoqiang

AU - Wierenga, Albertus T.J.

AU - Petraglia, Francesca

AU - Narang, Pankaj

AU - Janssen-Megens, Eva M.

AU - Mandoli, Amit

AU - Merkel, Angelika

AU - Berentsen, Kim

AU - Kim, Bowon

AU - Matarese, Filomena

AU - Singh, Abhishek A.

AU - Habibi, Ehsan

AU - Prange, Koen H.M.

AU - Mulder, André B.

AU - Jansen, Joop H.

AU - Clarke, Laura

AU - Heath, Simon

AU - van der Reijden, Bert A.

AU - Flicek, Paul

AU - Yaspo, Marie Laure

AU - Gut, Ivo

AU - Bock, Christoph

AU - Schuringa, Jan Jacob

AU - Altucci, Lucia

AU - Vellenga, Edo

AU - Stunnenberg, Hendrik G.

AU - Martens, Joost H.A.

PY - 2019/1/22

Y1 - 2019/1/22

N2 - 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.

AB - 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.

KW - acute myeloid leukemia

KW - AML

KW - chromatin states

KW - DNA accessibility

KW - epigenome

KW - histone marks

KW - stemness

KW - transcriptome

UR - http://www.scopus.com/inward/record.url?scp=85060104976&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2018.12.098

DO - 10.1016/j.celrep.2018.12.098

M3 - Article

C2 - 30673601

AN - SCOPUS:85060104976

SN - 2211-1247

VL - 26

SP - 1059-1069.e6

JO - Cell Reports

JF - Cell Reports

IS - 4

ER -

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

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