DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome—Relevance 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.

Assessment of Total Antioxidant Capacity, 8-Hydroxy-2′-deoxy-guanosine, the Genetic Landscape, and Their Associations in BCR::ABL-1-Negative Chronic and Blast Phase Myeloproliferative Neoplasms

“…Our findings detected an association between TAC and MPNs (OR = 1.82; p = 0.05), particularly in ET (OR = 2.36; p = 0.03) and PMF (OR = 2.11; p = 0.03), reinforcing the idea that derangements in the pro-oxidant/antioxidant equilibrium might trigger the onset of myeloid malignancies, e.g., MPNs, MDS, AML, and others, as previously hypothesized [27,28].…”

DNA methylation as an epigenetic mechanism in the regulation of LEDGF expression and biological response in aging and oxidative stress

“…2C ). It is known that the promoters with CpG island are the target for DNA methylation, and the methylation status regulates the expression of genes [ 50 ]. Increasing studies have shown that the magnitude of oxidative stress alters methylation/demethylation patterns of genes and their expression [ 45 , 51 , 52 ].…”

Micronutrient regulation of the DNA methylome

“…Prostate cancer models treated with vitamin E exhibit decreased DNMT protein expression and reduced CpG methylation at target loci of genes involved in cellular redox homeostasis such as the Nrf2 promoter (Huang et al, 2012a). As oxidative stress is often correlated with increased global levels of 5mC (Garcia-Guede et al, 2020;Goncalves et al, 2021), it is possible that vitamin E can reduce DNA methylation indirectly due to its antioxidant activity (Ryan et al, 2010;Zappe et al, 2018).…”