1- PhD Student, Department of Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran 2- Associate Professor, Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran , hamid143@yahoo.com 3- Assistant Professor, Department of Biology, Faculty of Biology Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran 4- Professor, Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran , Professor, Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Abstract: (166 Views)
Background: The evolution of resistance to imatinib and disease progression are multifactorial events in CML patients. These events are not only determined by BCR-ABL1 dependent pathway but also are involved a number of other genetic and epigenetic aberrations including DNA methylation. We aimed to investigate the role of DDIT3 (DNA-damage-inducible transcript 3) gene methylation in relation to respose to imatinib, CML progression, and also investigate the impact of the smoking on methylation level.
Materials and methods: 50 CML patients at different clinical stages of the disease (including 20 good response and 30 non-mutated imatinib resistant patients) and 15 health control were recruited for methylation levels evaluation of promoter DDIT3 gene by MS-HRM (Methylation Sensitive High Resolution Melt) analysis.
Results: There was significant difference in the mean (±standard deviation) of DDIT3 methylation percentage between two response groups (63.8±17.79 vs 47.75±14.18, P=0.002). DDIT3 promoter hypermethylation in 51-100% level indicated a higher risk for progression to advance phase (OR= 5.75; 95% CI: 1.40-23.49; P= 0.01) and imatinib resistance (OR= 8.5; 95% CI: 1.96-36.79; P= 0.004). Importantly, smokers were associated with a higher percentage of DDIT3 methylation (OR= 11.8; 95% CI, 2.67-52.67; P=0.001).
Conclusion: Our findings indicated that hypermethylation of DDIT3 gene is associated with imatinib resistance, CML progression and smoking. Further investigations on a more number is needed to confirm of these results that could be suggest as potential biomarker of disease progression and resistance to imatinib.
Foroutanjazi M, Hamid M, Salehi M, Hashemi M. Epigenetic silencing of DDIT3 gene and its relationship with imatinib resistance, disease progression and smoking status among patients with chronic myeloid leukemia. MEDICAL SCIENCES 2025; 35 (1) :14-23 URL: http://tmuj.iautmu.ac.ir/article-1-2181-en.html