Application of HRM Analysis in Detection of PDGFRA Exon 10 Polymorphism in CML Patients with Imatinib Resistance
https://doi.org/10.47836/mjmhs.18.5.18
- Author:
Nur Sabrina Abd Rashid
1
;
Sarina Sulong
1
;
Azlan Husin
2
;
Rosline Hassan
2
;
Mohamad Ros Sidek
1
;
Nazihah Mohd Yunus
1
Author Information
1. Human Genome Center, School of Medical Sciences, Health Campus Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia
2. Hemato-Oncology Unit and Department of Internal Medicine, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia
- Publication Type:Journal Article
- Keywords:
Chronic myeloid leukaemia, PDGFRA, Imatinib mesylate, polymorphism, HRM
- From:Malaysian Journal of Medicine and Health Sciences
2022;18(No.5):130-137
- CountryMalaysia
- Language:English
-
Abstract:
Introduction: Imatinib mesylate has been widely used as a standard treatment for chronic myeloid leukemia (CML).
It acts as a selective competitive inhibitor of the BCR-ABL tyrosine kinase. Despite the excellent efficacy on CML
treatment, some patients developed resistance to the treatment. Mutation in the PDGFRA may be one of the factors
involved in the mechanism of resistance that affects the response to imatinib. The mutational status of PDGFRA is
highly relevant for prognosis and treatment prediction in CML patients. Thus, this study is intended to establish and
validate a High Resolution Melting (HRM) analysis for PDGFRA exon 10 c.1432 T>C polymorphism in CML patients.
Methods: High resolution melting (HRM) analysis was used to identify the c.1432 T > C polymorphism in PDGFRA
exon 10 (n =86; response = 43; resistance = 43). The results from HRM analysis were compared and validated with
Sanger sequencing. The association between the polymorphism and treatment response was assessed by statistical
analysis using binomial logistic regression analysis. Results: HRM analyses showed two different melt curves. One
curve followed the shape of the reference, homozygous wild type (TT) and the other curve showed a different melting profile than the reference with the TC genotype (heterozygous variant). The results revealed that heterozygous
variant (TC) genotype showed a high risk of acquiring resistance with an OR of 3.795; 95% CI: 1.502-9.591, with
a statistically significant association, p = 0.005. HRM analysis also showed 100% sensitivity and specificity in the
detection of PDGFRA exon 10. Conclusion: The HRM analysis of PDGFRA exon 10 c.1432 T>C was successfully
established. The exon 10 c.1432 T>C polymorphism shows a higher risk for the development of resistance toward
imatinib treatment.
- Full text:11.2022my1337.pdf
