Clinical relevance of vascular endothelial growth factor (VEGFA) and VEGF receptor (VEGFR2) gene polymorphism on the treatment outcome following imatinib therapy

• Published in: Annals of oncology Vol. 21; no. 6; pp. 1179 - 1188
• Main Authors: Kim, D.H., Xu, W., Kamel-Reid, S., Liu, X., Jung, C.W., Kim, S., Lipton, J.H.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.06.2010; Oxford University Press
• Subjects: Adult; Aged; Aged, 80 and over; angiogenesis; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Benzamides; Biological and medical sciences; Biomarkers, Pharmacological - metabolism; chronic myeloid leukemia; Disease Progression; Female; Hematologic and hematopoietic diseases; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Piperazines - therapeutic use; Polymorphism, Single Nucleotide - physiology; Prognosis; Pyrimidines - therapeutic use; Retrospective Studies; single-nucleotide polymorphism; Treatment Outcome; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor Receptor-2 - genetics; VEGF; VEGFR2; Young Adult; VEGFR2; chronic myeloid leukemia; imatinib mesylate; single-nucleotide polymorphism; angiogenesis; VEGF; Antineoplastic agent; Prognosis; Genetic variability; Relevance; Myeloproliferative syndrome; Angiogenesis; Neovascularization; Vascular endothelial growth factor receptor 2; Protein-tyrosine kinase; Biological receptor; Imatinib; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; Chronic myelogenous leukemia; Genotype; Malignant hemopathy; Vascular endothelium growth factor; Treatment; Single nucleotide polymorphism; Cancer
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdp452

Imatinib could reverse marrow angiogenesis and decrease the plasma level of vascular endothelial growth factor (VEGF) in chronic myeloid leukemia (CML) patients. The current study investigated the impact of four vascular endothelial growth factor type A (VEGFA) and three vascular endothelial growth factor receptor type 2 (VEGFR2) gene polymorphisms on the outcomes of 228 CML patients following imatinib therapy. VEGFA genotypes such as -2578C>A (rs699947), -460T>C (rs833061), +405G>C (rs2010963) and +936C>T (rs3025039) loci and VEGFR2 genotypes (rs1531289, rs1870377 and rs2305948) were analyzed using matrix-assisted laser desorption/ionization time-of-flight-based method. In single marker analyses, strong correlations were noted between complete cytogenetic response (CCyR) and VEGFR2 genotypes (rs1531289/rs1870377), between treatment failure and VEGFR2 genotype (rs1870377) and between progression to advanced disease and VEGFA genotypes (rs699947/rs833061). Three haplotypes of VEGFR2 gene were generated as follows: GT (46.1%), AT (27.9%) and GA (25.7%). Haplotype analyses showed good correlations between VEGFR2 haplotype and CCyR and treatment failure to imatinib. Multivariate analyses confirmed strong correlations of VEGFR2 polymorphisms (especially rs1531289, rs1870377 or VEGFR2 haplotype) with CCyR, treatment failure and of VEGFA genotype (rs699947) with progression to advanced disease. The VEGFR2 gene polymorphism correlates with cytogenetic response, treatment failure following imatinib therapy for CML, while VEGFA genotype correlates with progression to advanced disease.