Down-regulation of cellular vascular endothelial growth factor levels induces differentiation of leukemic cells to functional leukemic-dendritic cells in acute myeloid leukemia

Abstract

We examined the effect of cellular vascular endothelial growth factor (VEGF) levels on the generation of leukemic dendritic cells (DCs). Leukemic DCs were successfully generated in vitro from bone marrow cells of 16 of 21 acute myeloid leukemia (AML) patients, and the cellular VEGF concentrations in the leukemic cells and the neutralization of VEGF with anti-VEGF antibody were determined. AML cells that failed to generate leukemic DCs showed significantly higher cellular VEGF levels compared with generated leukemic DCs, and down-regulation of cellular VEGF levels induced the generation of leukemic DCs from AML cells. Inhibition of cellular VEGF levels increased interleukin (IL)-12 production and the allostimulatory capacity of leukemic DCs. These results suggest that the generation of leukemic DCs from AML cells is inversely related to the VEGF production of the cells and that the down-regulation of cellular VEGF levels can induce potential differentiation of leukemic cells to functional leukemic DCs in patients with AML.

Keywords:

• Dendritic cell
• leukemia
• VEGF