Vascular Endothelial Growth Factor Receptor Polymorphisms and im Treatment Response in Chronic Myeloid Leukemia Patients

Abstract

Abstract Background Imatinib mesylate (IM) is the gold standard drug for chronic myeloid leukemia (CML) treatment. However, intrinsic and acquired resistance against IM has become a problem in CML treatment. Vascular endothelial growth factor receptor 2 (VEGFR2) plays a pivotal role in leukemia associated angiogenesis. Its expression is a good predictor of poor survival in CML. Genetic polymorphisms in VEGFR2 result in varied VEGFR2 expression and may lead to inter individual variation in disease progression and outcome to IM therapy. Aim of this study was to investigate the frequencies of VEGFR2 polymorphisms rs1531289 and rs2305948 in Malaysian CML patients and to determine the impact of these SNPs on IM treatment response in these CML patients. Methods DNA extracted from 230 CML patients (121 IM resistant and 109 IM good response) were genotyped using restriction fragment length polymorphism analysis and genotypes were categorized into homozygous wildtype, heterozygous and homozygous variants. The difference in genotype frequencies of the two SNPs, between the two groups of CML patients were compared using x2 test and the association between genotypes and treatment response was assessed using logistic regression analysis and deriving ORs with 95% CI. Results The SNP rs1531289 did not show any significant association with IM resistance. For rs2305948, the heterozygous variant genotype (CT) and variant allele (T) showed significant association with IM resistance (OR, 2.38; CI,1.33-4.25, p = 0.003 and OR,1.48; CI, 1.02-2.14,p=0.039 respectively). Haplotype analysis of the two SNPs did not show any association with treatment response. Conclusion VEGFR2 polymorphism rs2305948 which is associated with cytogenetic response and development of resistance to IM therapy might be a potential prognostic predictor of IM treatment response in CML patients. This study was financially supported by Research University Grant of Universiti Sains Malaysia, 2017.