European Journal of Molecular & Clinical Medicine

Abstract

Introduction: Chronic myeloid leukemia (CML) is a myeloproliferative disorder derived by formation of Philadelphia chromosome (Ph chromosome). Formation of the Ph chromosome is caused by a reciprocal translocation between the chromosomes 9 and 22 t(9;22)(q34;q11), resulting in a fusion protein known as BCR-ABL which has constitutive tyrosine kinase activity and promotes the proliferation of leukemia cells via multiple mechanisms. Vascular endothelial growth factor receptor types 2 (VEGFR2) gene single nucleotide polymorphisms have been detected in CML and evidence suggests its influence on leukemia susceptibility and outcome. Aim: To evaluate the polymorphism of VEGFR 2 gene among Iraqi CML patients, and the relation of the gene receptor polymorphism in response to treatment and prognosis. Material and Methods: the study included 80 subjects, 40 CML and 40 healthy control age and sex matched. Routine investigations were collected including clinical signs and symptoms, physical examination, CBC, liver function tests and BCR-ABL1 &/or FISH. Real time PCR technique was used to detect VEGFR-2 gene polymorphism with SaCycler 96 using genomic DNA extracted from peripheral blood and TaqMan SNPs genotyping assay ((rs1531289, rs1870377 and rs2305948))for both patients and controls. Results: VEGFR-2 polymorphisms SNP1 (rs1531289 T>C) in CML patients presented with 82.5% showing the variant genotypes and 17.5% showing the wild homozygous genotype, while control showed 80% variant genotypes and 20 % wild genotype ,SNP2 (rs1870377 T>A) in CML patients presented with 80% showing the homozygous wild genotype and 20% showing the variant genotypes ,while control showed 62.5% the homozygous wild genotype and 37.5% showing the variant genotypes;SNP3 (rs2305948)in CML patients presented with showed 97.5% the homozygous wild genotype and 2.5% showing the variant genotypes while control showed 87.5% the homozygous wild genotype and 12.5% showing the variant genotypes P-values (0.4,0.004 and 0.09 respectively) .60% of CML patients who showed Molecular response were related to the heterozygous variant genotype of SNP (rs1531289 T>C) of VEGFR-2 Polymorphism, while 55% of patients with molecular response were related to the wild homozygous genotype of (rs1870377 T>A)and 70 % of patients with molecular response were related to the wild homozygous genotype of (rs2305948 C>T).Conclusion: VEGFR-2 polymorphism is common among Iraqi CML patients and might impose a high risk of CML development and influence treatment response.