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

Volume 13 , Issue 3 , September 2023

Authors

Alan Namiq Mahmud 1 ; Dlnya Asad Mohamad 2 ; Mohammad Hamid 3

1 Shar Hospital, Kurdistan Region, Iraq.

2 College of Science, University of Sulaimani, Kurdistan Region, Iraq.

3 Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

DOI logo 10.17656/jsmc.10417

Keywords

Abstract

Background
Chronic 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.
Objectives
This 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 Methods
Blood 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.
Results
The 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%.
Conclusion
The 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.

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  • Published at21 September 2023

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