The clinical values of dysregulated DNA methylation and demethylation intermediates in acute lymphoblastic leukemia.

DNA methylation is a well-known epigenetic modification, and it can be iteratively oxidized to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC). Acute lymphoblastic leukemia (ALL) is a severe hematological disease, and it is essential to find out new biomarkers to better diagnose and cure ALL due to the development of chemo-resistance and low cure rate in adult ALL. This study aims to describe the role of global methylation and demethylation intermediates in ALL. The levels of global methylation and its oxidation products in the peripheral blood (PB) of ALL patients and healthy controls were determined by Enzyme-Linked Immunosorbent Assay (ELISA). In this study, we described that global 5-mC, 5-hmC and 5-fC levels were dysregulated in ALL, and they were associated with clinical characteristics and genetic abnormalities of ALL patients. Interestingly, 5-mC and 5-hmC were closely related to inflammation, and the levels of 5-hmC were inversely correlated with C-Reactive protein (CRP) and ferritin. Finally, 5-mC and 5-hmC were associated with complete remission (CR), and 5-hmC was revealed as an independent prognostic indicator for ALL. This study described a novel role for global methylation and demethylation intermediates in ALL detection and prognosis, and provided new clue to distinguish high-risk patients and improve the curative effect on ALL patients.