METHYLATION PATTERN OF THE RUNX3 GENE AND ITS IMPACT ON RESPONSE TO IMATINIB THERAPY IN CHRONIC MYELOID LEUKEMIA

Abstract

BackgroundChronic Myelogenous Leukemia (CML) is a clonal stem cell disease with deregulated tyrosine kinase activity of BCR-ABL. DNA methylation in gene promoters influences disease development, therapeutic response, and clinical outcome in various diseases.
 ObjectivesThis study aimed to investigate the methylation pattern in promoter regions of the runt-related transcription factor 3 (RUNX3) gene and its effect on the response to imatinib therapy, among CML patients.
 Patients and MethodsBlood samples were collected from 100 participants from November 2020 to February 2022, in two groups 75 samples of CML patients and 25 samples of healthy controls, genomic DNA was extracted from the samples by using the salting-out method, then Isolated DNA was treated with sodium bisulfite. By Methylation-Sensitive High-Resolution Melting (MS-HRM), the samples were analyzed.
 ResultsThe promoter sequence methylation level is significantly higher (P<0.05) in DNA samples from CML patients than in the control group, the methylation level in most of the healthy control samples 96% was detected between 0-24% while in CML patients was 16%, in 25-49%, RUNX3 methylation levels in Health individuals were 4%, moreover in CML patients were 24% also, in 50-100% of methylation level, health control was 0%, in CML patient showed 60%. According to methylation detection of RUNX3 among Imatinib resistance and good response, the results of IM resistance were detected between 0-40% was 15.21%, Furthermore, in good response was 79.31%. In other hand at 41-100% RUNX3 methylation levels in IM resistance was 84.78%, while a good response was recorded at 20.68%.
 ConclusionThe study concluded that RUNX3 gene hypermethylation often occurs in CML patients. Additionally, there is a strong correlation between RUNX3 hypermethylation and poor imatinib respondents. We found that both IM resistance and CML patients have higher levels of RUNX3 gene hypermethylation. Moreover, research on a larger sample size is required to validate these findings, which may serve as possible indicators of disease progression and imatinib resistance.