Author(s): Gonçalves, Ana Cristina ; Alves, Raquel ; Baldeiras, Inês ; Marques, Bárbara ; Oliveiros, Bárbara ; Pereira, Amélia ; Costa, José Manuel Nascimento ; Cortesão, Emília ; Vieira, Luísa Mota ; Ribeiro, Ana Bela Sarmento
Date: 2021
Persistent ID: https://hdl.handle.net/10316/95820
Origin: Estudo Geral - Universidade de Coimbra
Subject(s): DNA methylation; Acute myeloid leukemia; Blood biomarkers; Myelodysplastic syndrome; Oxidative stress; Prognosis; Progression; Survival
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.
The present work was supported by CIMAGO (Center of Investigation on Environment Genetics and Oncobiology), Faculty of Medicine, University of Coimbra, Portugal; by a grant from Santander-Totta Bank/Gabinete de Apoio/Investigação (GAI) of the Faculty of Medicine, University of Coimbra, Portugal; and by the Foundation for Science and Technology (FCT), Portugal
