DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome—Relevance as Complementary Prognostic Biomarkers

SIMPLE SUMMARY: Myelodysplastic syndrome (MDS) is a hematological malignancy with a high propensity to evolve to acute myeloid leukemia. Oxidative stress and abnormal DNA methylation are important in this neoplasia’s development and progression. We investigate whether oxidative stress parameters were correlated with localized and global DNA methylations in the peripheral blood of patients with MDS. We found that oxidative stress was positively correlated with DNA methylation and associated with worse overall survival. Biologically, these facts suggest a relationship between oxidative stress and DNA methylation, two common pathogenic mechanisms involved in MDS. Clinically, our findings can improve an MDS patient’s management if used as complementary prognostic biomarkers. ABSTRACT: Oxidative stress and abnormal DNA methylation have been implicated in cancer, including myelodysplastic syndromes (MDSs). This fact leads us to investigate whether oxidative stress is correlated with localized and global DNA methylations in the peripheral blood of MDS patients. Sixty-six MDS patients and 26 healthy individuals were analyzed. Several oxidative stress and macromolecule damage parameters were analyzed. Localized (gene promotor) and global DNA methylations (5-mC and 5-hmC levels; LINE-1 methylation) were assessed. MDS patients had lower levels of reduced glutathione and total antioxidant status (TAS) and higher levels of peroxides, nitric oxide, peroxides/TAS, and 8-hydroxy-2-deoxyguanosine compared with controls. These patients had higher 5-mC levels and lower 5-hmC/5-mC ratio and LINE-1 methylation and increased methylation frequency of at least one methylated gene. Peroxide levels and peroxide/TAS ratio were higher in patients with methylated genes than those without methylation and negatively correlated with LINE-1 methylation and positively with 5-mC levels. The 5-hmC/5-mC ratio was significantly associated with progression to acute leukemia and peroxide/TAS ratio with overall survival. This study points to a relationship between oxidative stress and DNA methylation, two common pathogenic mechanisms involved in MDS, and suggests the relevance of 5-hmC/5-mC and peroxide/TAS ratios as complementary prognostic biomarkers.