Angiogenic factors in multiple myeloma: higher levels in bone marrow than in peripheral blood

BACKGROUND AND OBJECTIVES: To study the role of some soluble factors in the process of angiogenesis that accompanies multiple myeloma (MM). DESIGN AND METHODS: The concentrations of three well-known angiogenic peptides, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF) were evaluated by an ELISA method. All of these factors were measured in the plasma obtained from peripheral blood (PB) and bone marrow (BM) aspirates of 34 patients affected by plasma cell disorders. This series included one patient with a solitary extramedullary plasmacytoma, 17 patients with MM at diagnosis, and 16 with previously treated MM. RESULTS: In all the patients, the concentration of each angiogenic factor was higher in bone marrow than in peripheral blood. Mean values of the three angiogenic factors in BM or in PB were lower in stage I than stage II-III. One patient with extramedullary solitary myeloma had high levels of VEGF and bFGF but this increase was not found in the other 6 patients with extramedullary disease when compared with patients without extramedullary disease. VEGF and bFGF did not correlate with each other while HGF showed a weak correlation with VEGF and a stronger one with bFGF. Moreover, VEGF correlated with features of disease activity, such as C-reactive protein, and 2-microglobulin, while both bFGF and HGF showed an inverse correlation with albumin level. No correlation was found between VEGF, bFGF and HGF levels and age, M protein level, osteolytic lesions, or percentage of BM plasma cells. Since angiogenic factors may be released by normal cells in response to hypoxia, we also evaluated erythropoietin (EPO) levels (which correlate with the hypoxic stimulus) both in PB and BM plasma of these patients but none of the measured angiogenic factors correlated with EPO levels. Interpretation and Conclusions. Several soluble factors may play a role in the angiogenic activity described in MM but their contribution to the progression of disease may be different. The finding of higher levels of these factors in BM than in PB might indicate that the bone marrow environment is their major source. Concentrations of angiogenic factors parallel the activity of disease and are independent of the hypoxic stimulus.