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

Musa Düdükcü,Rahşan Yıldırım,Leylagül Kaynar,İlhami Kiki,Gülden Sincan,Fuat Erdem,Mustafa Çetin,Çiğdem Pala,Ömer Topdağı,Mehmet Gündoğdu,Selin Merih Urlu

doi:10.15197/ejgm.1527

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.

Highlights

Angiogenesis is a formation of new capillaries from blood vessels
Imatinib, Nilotinib and Dasatinib were not superior to each other regarding to serum vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR-1), but it may be said that Nilotinib may has slightly more effect on inhibition of anjiogenesis
The target of most angiogenesis inhibitors has been directed to the VEGF signaling pathway, such as the monoclonal antibody bevacizumab and two kinase inhibitors Sunitinib and Sorafenib

Summary

Introduction

Angiogenesis is a formation of new capillaries from blood vessels It plays an important role in the progression and prognosis of solid tumors. There are members of the fibroblast growth factor family, vascular endothelial cell growth factor, IL-8, epidermal growth factor, platelet derived endothelial cell growth factor, angiogenin, angiotropin, tumor necrosis factor and others [3]. The most potent stimulating cytokines of angiogenesis are vascular endothelial growth factor (VEGF) and basic fibroblast growth factor [4,5,6]. It was found that expression of VEGF protein increased some hematological malignancies [10]. In newly diagnosed patients with a range of FAB types of acute myeloblastic leukemia (AML), there is a direct relationship between increasing cellular VEGF content and shorter survival [13]. The binding of VEGF-A to VEGF receptor 1 (VEGFR-1) induces endothelial cell migration [15]

Methods

Results

Conclusion