Differential expression of vascular endothelial growth factors and their receptors in multiple myeloma

Division of Hematology, Department of Internal Medicine, Mayo Clinic 200 First St SW, Rochester, MN 55905, USA.

BACKGROUND AND OBJECTIVES: Bone marrow angiogenesis is increased in patients with multiple myeloma (MM) and correlates with disease stage. DESIGN AND METHODS: Previous studies of quantifying vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) in plasma cells from patients at different stages of MM found no significant difference in expression between overt MM and earlier pre-malignant stages of the disease namely, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). RESULTS: In this report we used quantitative flow cytometry to study cytoplasmic VEGF (cyVEGF) expression (measured as antibody binding capacity) in plasma cells from patients with MM (n = 22), MGUS/SMM (n = 12), and AL-amyloidosis (AL) (n = 9). CyVEGF expression was higher in MM (169,591) than in MGUS/SMM (144,858), or AL (106,011) although these differences were not statistically significant. Using an indirect VEGFR assay that measures VEGF binding, we found VEGF receptors on plasma cells from all groups of patients, with the lowest expression on plasma cells from normal individuals. We detected VEGF R1, VEGF R2, and VEGF R3 on plasma cells from all groups of patients and found receptor expression predominantly in the subset of CD45-positive plasma cells. INTERPRETATION AND CONCLUSIONS: This study supports the concept that VEGF is involved in the pathogenesis of MM, and suggests that VEGF may differentially affect a subset of plasma cells.