Expression Changes of SIRT1 and FOXO3a Significantly Correlate with Oxidative Stress Resistance Genes in AML Patients.

Abstract

The increased metabolism in acute myeloid leukemia (AML) malignant cells resulted in the production of high levels of free radicals, called oxidative stress conditions. To avoid this situation, malignant cells produce a considerable amount of antioxidant agents, which will lead to the release of a continuous low level of reactive oxygen species (ROS), causing genomic damage and subsequent clonal evolution. SIRT1 has a key role in driving the adaptation to this condition, mainly through the deacetylation of FOXO3a that affects the expression of oxidative stress resistance target genes such as Catalase and Manganese superoxide dismutase (MnSOD). The aim of this study is to simultaneously investigate the expression of SIRT1, FOXO3a, and free radical-neutralizing enzymes such as Catalase and MnSOD in AML patients and measure their simultaneous change in relation to each other. The gene expression was analyzed using Real Time-PCR in 65 AML patients and 10 healthy controls. Our finding revealed that expression of SIRT1, FOXO3a, MnSOD and Catalase was significantly higher in AML patients in comparison to healthy controls. Also, there was a significant correlation between the expression of SIRT1 and FOXO3a, as well as among the expression of FOXO3a, MnSOD and Catalase genes in patients. According to the results, the expression of genes involved in oxidative stress resistance was higher in AML patients, which possibly contributed to the development of malignant clones. Also, the correlation between the expression of SIRT1 and FOXO3a gene reflects the importance of these two genes in increased oxidative stress resistance of cancer cells.