@article{e9c77b85813847498496a024600f98e2,
title = "DNA Methylation Signatures Identify Biologically Distinct Subtypes in Acute Myeloid Leukemia",
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).",
keywords = "CELLCYCLE, DNA, HUMDISEASE",
author = "Figueroa, {Maria E.} and Sanne Lugthart and Yushan Li and Claudia Erpelinck-Verschueren and Xutao Deng and Christos, {Paul J.} and Elizabeth Schifano and James Booth and {van Putten}, Wim and Lucy Skrabanek and Fabien Campagne and Madhu Mazumdar and Greally, {John M.} and Valk, {Peter J.M.} and Bob L{\"o}wenberg and Ruud Delwel and Ari Melnick",
note = "Funding Information: The authors are indebted to the colleagues of the bone marrow transplantation group and the molecular diagnostics laboratory of the department of Hematology at Erasmus University Medical Center (Erasmus MC) for storage of samples, molecular analysis, and in vitro culture of leukemia cells. This work was supported by grants from the National Institutes of Health to R.D. (CA118316); a grant from the Dutch Cancer Society “Koningin Wilhelmina Fonds” to R.D., P.J.M.V., and B.L (EMCR 2006-3522), and a grant from ErasmusMC (MRace) to R.D. S.L is supported by a EHA research fellow ship, {\textquoteleft}AGIKO{\textquoteright} fellowship of ZonMW and the Dutch Cancer Society “Koningin Wilhelmina Fonds.” M.E.F. was partially supported by the SASS Foundation Research Fellowship award and by an ASH Fellow Scholar Award. A.M. is supported by NCI R01 CA104348, the Chemotherapy Foundation, the Sam Waxman Cancer Research Foundation, and the G&P Foundation and is a Leukemia and Lymphoma Society Scholar. J.M.G. is supported by a grant from the National Institutes of Health (NIH) (R01 HD044078). F.C. is supported by an Institutional Clinical and Translational Science Award RFA-RM-07-002 and resources from the David A. Cofrin Center for Biomedical Information at Weill Cornell. J.B. is partially supported by an NSF grant: NSF-DMS 085865. P.J.C. and M.M. are supported by a Clinical Translational Science Center (CTSC) Grant (UL1-RR024996). M.E.F., J.M.G., R.D., and A.M. conceived and designed the research; M.E.F., Y.L., and C.E.V. performed the research; M.E.F., S.L., L.S., P.C., X.D., M.M., F.C., E.S., J.B., R.D., and A.M. analyzed the data; B.L., P.J.V., and R.D. contributed research material; B.L., P.J.V., W.V.P., and J.M.G. contributed to data interpretation; M.E.F., S.L., B.L., R.D., and A.M. wrote the manuscript. ",
year = "2010",
month = jan,
day = "19",
doi = "10.1016/j.ccr.2009.11.020",
language = "English (US)",
volume = "17",
pages = "13--27",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "1",
}
