Bone marrow stromal cell-derived vascular endothelial growth factor (VEGF) rather than chronic lymphocytic leukemia (CLL) cell-derived VEGF is essential for the apoptotic resistance of cultured CLL cells.

摘要: Chronic lymphocytic leukemia (CLL) cells feature a pronounced apoptotic resistance. The vascular endothelial growth factor (VEGF) possesses role in this block, although underlying functional mechanisms and the involvement of microenvironment are unclear. In study, VEGF status CLL was assessed by enzyme-linked immunosorbent assay immunofluorescence. receptor 2 (VEGFR2) phosphorylation determined flow cytometrically For co-culture, were cultivated on monolayer bone marrow-derived stromal cell (BMSC) line HS5. Secreted neutralized using monoclonal antibody mAb293 (R&D Systems, Minneapolis, MN, USA). To block protein secretion, we used Brefeldin A. downregulated BMSCs small interfering RNA (siRNA), survival annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. express secrete possess phosphorylated VEGFR2. This positive is not sufficient to prevent spontaneous apoptosis vitro. Coculture with BMSCs, which vast amounts VEGF, maintains vitro survival. Blockage secreted significantly reduced support for cocultured cells. Both general blockage secretion A but cells, siRNA-mediated downregulation coculture-mediated It can be concluded that BMSC-derived proteins particular, cell-derived essentially involved Hence, therapeutic targeting signaling might promising approach overcome resistance within their natural microenvironment.