Synergistic effect of vascular endothelial growth factor and angiopoietin-2 on progression free survival in multiple myeloma

Abstract

Bone marrow neoangiogenesis plays an important role in multiple myeloma (MM) and depends on the interplay of angiogenic cytokines. We investigated the levels of angiogenic cytokines such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiopoietin (Ang)-1, Ang-2 and hypoxia inducible factor-1 alpha (HiF-1α) in MM patients and their association with treatment outcome. Serum levels and mRNA expression of VEGF, Ang-2, Ang-1, bFGF and HiF-1α were evaluated in 71 MM patients using enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction. In multivariate Cox regression analysis, serum levels of VEGF ≥ 756 pg/ml (HR 2.2, 95% CI 1.02–4.91; p = 0.045) and relative mRNA expression levels of Ang-2 ≥ 0.93 (HR 21.0, 95% CI 6.27–70.45; p < 0.001) were predictive of inferior progression free survival (PFS) and patients with concomitant increase in VEGF and Ang-2 had poor outcome compared to the rest of the patients (HR 32.6, 95% CI 7.20–148.36; p < 0.001). These results suggest that VEGF and Ang-2 act in synergy and their expression levels at presentation are predictive of PFS in MM.