Deregulation of mitochondrial sirtuins and OGG1-2a acts as a prognostic and diagnostic biomarker in leukemia.

Abstract

Purpose: The present study was planned to explore the expression variations of mitochondrial sirtuins and the mitochondrial DNA repair enzyme OGG1-2a in leukemia patients. Oxidative stress and deacetylation levels of leukemia patients were measured in the present study. Methods: A total of 200 leukemia patients along with 200 healthy controls were evaluated using quantitative PCR, 8OXOG assay and deacetylation assay. Results: Significant deregulation of SIRT3 (p<0.0001), SIRT4 (p<0.0001), SIRT5 (p<0.0001), Ki-67 (p<0.0001) and OGG1-2a (p<0.0001) was detected in patients versus controls. Survival analysis showed that deregulation of said genes was associated with decreased survival of leukemia patients (SIRT3: p<0.004; SIRT4: p<0.0009; SIRT5: p<0.0001; OGG1-2a: p<0.03). Receiver operating characteristic curve analysis confirmed the diagnostic values of selected genes in leukemia patients. Levels of 8OXOG adducts were measured, and significantly increased 8OXOG adduct levels were observed in patients versus controls. Conclusion: These data suggest that deregulation of SIRT3, SIRT4, SIRT5 and OGG1-2a acts as a diagnostic and prognostic marker in leukemia.