Methylation of DNA Repair Genes as a Prognostic Biomarker in AML of a TCGA-LAML Cohort

Background: Dysregulation of DNA damage response and altered DNA methylation in acute myeloid leukemia (AML) have been reported, but the impact of methylation of DNA repair genes has not yet been researched. We aimed to predict the prognosis of non-APL AML patients based on the known CpG site methylation levels of DNA repair genes through The Cancer Genome Atlas AML project (TCGA-LAML). Methods: We utilized TCGA-LAML cohort (174 non-APL AML) for the methylation data of 22 DNA repair genes. Results: In univariate analysis among 174 non-APL AML patients of the TCGA-LAML cohort, the hypermethylation of MLH1, RAD51, and ATM showed superior overall survival (OS) than non-hypermethylated groups, while hypermethylation of RAD23A, RAD23B, MLH1, MSH2, BRCA1, BRCA2, RAD50, and PARP1 was associated with poor OS. We demonstrated that CpG hypermethylation levels of DNA repair genes differed according to the AML cytogenetic risk groups. In multivariate analysis, hypermethylation of MLH1 and RAD51 showed better OS than non-hypermethylated patients, but hypermethylation of MSH2 and RAD50 showed worse OS than non-hypermethylated patients. Conclusion: Methylation of 4 DNA repair genes, such as MLH1, RAD51, MSH2, and RAD50, have the potential to be independent risk factors in non-APL AML patients.