Effects of vascular endothelial growth factor on acute myelogenous leukemia blasts.

Vascular endothelial growth factor (VEGF) and its specific receptors are expressed by various malignant cells, including acute myelogenous leukemia (AML) blasts. In this study we performed a detailed characterization of VEGF effects on native human AML blasts derived from a large group of consecutive AML patients with high blast counts in peripheral blood. Exogenous VEGF had divergent effects on spontaneous proliferation and cytokine-dependent (GM-CSF, G-CSF, IL-3) proliferation. Increased, decreased, or unaltered proliferation was observed in the presence of VEGF for various patients, and the VEGF effect differed even in the same patient depending on which exogenous cytokine being present together with VEGF. Similarly, increased, decreased or unaltered interleukin-1beta (IL-1beta) and IL-6 secretion was detected when VEGF was added, and for certain patients the effect of VEGF differed between IL-1beta and IL-6. Exogenous VEGF could also modulate proliferation and differentiation of clonogenic AML progenitors. Constitutive AML blast secretion of VEGF was detected for 40% of patients. Leptin, Flt3-L, IL-4, IL-10, and IL-13 had divergent effects on VEGF release by AML blasts. These results suggest that VEGF can modulate AML blast functions in vivo for a subset of patients. Furthermore, the detection of VEGF in peripheral blood stem cell (PBSC) autografts suggests that VEGF may influence the proliferation and possibly also the survival of contaminating AML cells in PBSC autografts. We conclude that VEGF may influence the functional characteristics of AML cells. Our results suggest that VEGF is important in leukemic hematopoiesis, and the detection of VEGF in PBSC autografts indicates that VEGF may influence the functional phenotype of contaminating AML cells in these grafts.