The methylome of pediatric acute myeloid leukemia

10027 Background: DNA methylation can alter gene expression by either creating binding sites for methylation-dependent repressor proteins, or by disrupting the binding of transcription factors to their target sequences. DNA methylation has been studied extensively and associated with survival in adults with AML. However, a detailed genome-wide study of epigenetic regulation of gene expression and its pharmacological and clinical impact in pediatric AML patients has not been performed. Methods: In this study, we obtained Illumina 450K methylation array profiles for 175 pediatric patients and Affymetrix U133A gene expression arrays for 166 pediatric patients treated in the multicenter AML02 clinical trial (NCT00136084). Results: We found a very significant canonical correlation of methylation with expression (FDR ≤ 0.01) in 1,978 genes with several of the top ranked genes having established roles in the biology and treatment of AML. An analysis adjusting for risk group found that the canonical correlation m...