Successful Treatment with Imatinib Mesylate Significantly Decreases Plasma Levels of Vascular Endothelial Growth Factor (VEGF) and Soluble Endoglin (sCD105) but Not Basic Fibroblast Growth Factor (bFGF) or Angiopoietin-2 (Ang-2) in Patients with Chronic Myeloid Leukemia (CML) in Chronic Phase

Abstract

Introduction: Angiogenesis is an essential process in the biology of solid tumors as well as hematological malignancies. Several studies have recently reported increased markers of angiogenesis in chronic myeloid leukemia (CML). However, much less is known on the possible impact of tyrosine kinase inhibitor imatinib mesylate (IM), the current cornerstone of CML treatment, on angiogenic signaling.Aims: To analyze peripheral blood levels of angiogenic cytokines in patients with newly diagnosed CML and during imatinib treatment. Methods: Peripheral blood plasma concentrations of key angiogenic activators, namely vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), soluble endoglin (sCD105), and angiopoietin-2 (Ang-2) were quantified using commercially available sandwich enzyme-linked immunosorbent assay (ELISA) in 27 patients with chronic-phase CML and 80 healthy blood donors; furthemore, repeated samples during the therapy with IM were analyzed.Results: We detected significantly elevated levels of VEGF (p<0.0001), bFGF (p=0.026), and sCD105 (n=25, p<0.0001) in comparison to the control group. Elevation of Ang-2 was of borderline significance (n=14, p=0.051). Levels of VEGF and sCD105 significantly decreased in patients who achieved complete cytogenetic response (p<0.0001 and p=0.01) whereas bFGF or Ang-2 did not change significantly (p=0.978 and p=0.625, respectively). VEGF and sCD105 remained low in repeated samples taken during IM treatment. Interestingly, there was a trend towards higher VEGF in patients who did not achieve complete cytogenetic response (p=0.058).Conclusions: Peripheral blood levels of angiogenic activators VEGF, bFGF and sCD105 (and borderline Ang-2) were elevated in CML patients. Successful treatment with IM resulted in significant and durable suppression of circulating VEGF and sCD105 but not bFGF and Ang-2. Our results point to the potential significance of angiogenic signaling (especially VEGF pathway) in CML biology. Further research in this field is therefore highly desirable.