May Gender Have an Impact on Methylation Profile and Survival Prognosis in Acute Myeloid Leukemia

DNA methylation alteration is crucial for the initiation and development of Acute Myeloid Leukemia. However, only a few epigenetic biomarkers of AML have been discovered so far. DNA methylation of CpG rich gene promoters has the highest impact on gene expression level, so biomarkers should be sought in these genomic regions. Principal Component Analysis of methylation level reveals that male and female AML patients differ in CpG rich-gene promoters. Statistical comparison between males and females conducted for each CpG site confirms statistical relevance of differences only in CpG-rich promoter regions. P-value integration results in detection of AML-specific hypermethylated genomic regions and shows that almost 10% of CpG-rich promoters are differentially methylated between males and females. Functional analysis of genes with differentially methylated promoters in AML results in 322 enrichments for women and 1893 for men. Genes are mainly related to homeobox, cell development and morphogenesis. Survival analysis indentifies gender-specific potential epigenomic prognostic markers. Dissimilarity of the survival-significant gene sets between males and females is 75%.