Study of the association between HDAC8, SIRT1, and P53 gene expression with drug resistance in chronic myeloid leukemia patients

Chronic Myeloid Leukemia (CML) is characterized by the BCR-ABL fusion gene, which encodes the tyrosine kinase of BCR-ABL. Developing tyrosine kinase inhibitors (TKIs) can specifically inhibit the BCR-ABL oncoprotein and cure CML. However, problems such as drug resistance to this targeted therapy make for therapeutic failure and relapse. This study investigated the expression of histone deacetylase 8 (HDAC8), Sirtuin 1 (SIRT1), and P53 genes with drug resistance in chronic myeloid leukemia patients. In this study, 50 CML patients were divided into two groups: drug-resistant and drug-sensitive patients, and 50 healthy individuals were included as controls. After extracting RNA from the blood samples and quality assessment, cDNA was synthesized, and then a real-time polymerase chain reaction (Real-Time PCR) method was performed to check the expression of HDAC8, SIRT1, and P53 genes. Finally, statistical analysis was performed using SPSS version 25 and Stata software. The expression of the SIRT1 gene in drug-resistant patients was significantly higher than in CML patients who were drug-sensitive and also in the control group (p < 0.001). Our results showed a lower value of ΔCT for the p53 gene than the SIRT1 gene in drug-resistant patients. However, p53 gene expression was not significantly different between drug-sensitive and drug-resistant groups (p = 0.593). We observed that CML patients had significantly higher expression of the HDAC8 gene than the control subjects (p < 0.001). Our results suggested a probable association between perturbations of SIRT1, HDAC8, and P53 gene expression with the pathogenesis of CML. Also, SIRT1 and HDAC8 gene expression might have regulatory roles in optimal response to targeted therapy in CML patients.