TitleDNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia.
Publication TypeJournal Article
Year of Publication2010
AuthorsFigueroa, Maria E., Lugthart Sanne, Li Yushan, Erpelinck-Verschueren Claudia, Deng Xutao, Christos Paul J., Schifano Elizabeth, Booth James, van Putten Wim, Skrabanek Lucy, Campagne Fabien, Mazumdar Madhu, Greally John M., Valk Peter J. M., Löwenberg Bob, Delwel Ruud, and Melnick Ari
JournalCancer Cell
Date Published2010 Jan 19
KeywordsBiomarkers, Tumor, DNA Methylation, Epigenesis, Genetic, Female, Gene Expression Profiling, Humans, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute, Male, Middle Aged, Nucleophosmin, Prognosis

<p>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).</p>

Alternate JournalCancer Cell
PubMed ID20060365
PubMed Central IDPMC3008568
Grant ListUL1 RR024996-01 / RR / NCRR NIH HHS / United States
CA118316 / CA / NCI NIH HHS / United States
UL1-RR024996 / RR / NCRR NIH HHS / United States
R01 HD044078 / HD / NICHD NIH HHS / United States
R01 CA104348 / CA / NCI NIH HHS / United States
UL1 RR024996 / RR / NCRR NIH HHS / United States
R01 CA118316 / CA / NCI NIH HHS / United States