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

Research output: Contribution to JournalArticleAcademicpeer-review

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1059-1069.e6
JournalCell Reports
Volume26
Issue number4
DOIs
Publication statusPublished - 22 Jan 2019

Keywords

  • AML
  • DNA accessibility
  • acute myeloid leukemia
  • chromatin states
  • epigenome
  • histone marks
  • stemness
  • transcriptome

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