Effects of Imatinib, Nilotinib, Dasatinib on VEGF and VEGFR-1 Levels in Patients with Chronic Myelogenous Leukemia

Abstract

Objective: Vascular endothelial growth factor (VEGF) is a protein that binding to VEGF receptors 1 (VEGFR-1) and accelerates angiogenesis. The relationship between angiogenesis and progression of tumors were observed in both solid and hematologic cancers. Monoclonal antibodies capable of inhibiting angiogenesis, tyrosine kinase inhibitors use for haematological cancer treatment. In this study; we investigated the effects of Imatinib mesylate (STI-571; Gleevec), Nilotinib (AMN107; Tasigna) and Dasatinib (BMS-354825; Sprycell) on serum levels of VEGF and VEGFR-1, in patients with chronic phase of chronic myeloid leukemia (CML). Method: Serum levels of VEGF and VEGFR-1 were measured in 65 patients with chronic phase of CML. Serum VEGF and VEGFR-1 levels were determined using quantitative sandwich enzyme immunoassay technique according to the manufacturers’ instructions. Results: There were 33 (51%) male and 32 (49%) female patients in this study. 38 of 65 patients were using Imatinib, 15 Nilotinib, 12 Dasatinib. Mean serum VEGF and VEGFR-1 levels for the 65 patients with CML were 172.21±127.46 pg/mL and 199.62±122.22 pg/mL, respectively. In Dasatinib and Imatinib group, serum VEGF and VEGFR-1 levels were significantly higher than in control group (p= 0.008, p< 0.0001, and p< 0.0001, p< 0.0001). In Nilotinib group, serum VEGF levels were higher than control group, but; it was not statistically significant (p= 0.06) while. VEGFR-1 levels were significantly higher than those of controls (p< 0.0001). Conclusion: Imatinib, Nilotinib and Dasatinib were not superior to each other regarding to serum VEGF and VEGFR-1, but it may be said that Nilotinib may has slightly more effect on inhibition of anjiogenesis.