DNA Methylation Signatures Identify Biologically Distinct Subtypes in Acute Myeloid Leukemia

Maria E. Figueroa, Sanne Lugthart, Yushan Li, Claudia Erpelinck-Verschueren, Xutao Deng, Paul J. Christos, Elizabeth Schifano, James Booth, Wim van Putten, Lucy Skrabanek, Fabien Campagne, Madhu Mazumdar, John M. Greally, Peter J.M. Valk, Bob Löwenberg, Ruud Delwel, Ari Melnick

Research output: Contribution to journalArticle

562 Scopus citations

Abstract

We hypothesized that DNA methylation distributes into specific patterns in cancer cells, which reflect critical biological differences. We therefore examined the methylation profiles of 344 patients with acute myeloid leukemia (AML). Clustering of these patients by methylation data segregated patients into 16 groups. Five of these groups defined new AML subtypes that shared no other known feature. In addition, DNA methylation profiles segregated patients with CEBPA aberrations from other subtypes of leukemia, defined four epigenetically distinct forms of AML with NPM1 mutations, and showed that established AML1-ETO, CBFb-MYH11, and PML-RARA leukemia entities are associated with specific methylation profiles. We report a 15 gene methylation classifier predictive of overall survival in an independent patient cohort (p < 0.001, adjusted for known covariates).

Original languageEnglish (US)
Pages (from-to)13-27
Number of pages15
JournalCancer Cell
Volume17
Issue number1
DOIs
StatePublished - Jan 19 2010
Externally publishedYes

Keywords

  • CELLCYCLE
  • DNA
  • HUMDISEASE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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  • Cite this

    Figueroa, M. E., Lugthart, S., Li, Y., Erpelinck-Verschueren, C., Deng, X., Christos, P. J., Schifano, E., Booth, J., van Putten, W., Skrabanek, L., Campagne, F., Mazumdar, M., Greally, J. M., Valk, P. J. M., Löwenberg, B., Delwel, R., & Melnick, A. (2010). DNA Methylation Signatures Identify Biologically Distinct Subtypes in Acute Myeloid Leukemia. Cancer Cell, 17(1), 13-27. https://doi.org/10.1016/j.ccr.2009.11.020