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 pepti des, vascular endothelial growth factor (VEGF), basic fibroblast growth fac tor (bFGF), and hepatocyte growth factor (HGF) were evaluated by an ELISA m ethod. All of these factors were measured in the plasma obtained from perip heral blood (PB) and bone marrow (BM) aspirates of 34 patients affected by plasma cell disorders. This series included one patient with a solitary ext ramedullary plasmacytoma, 17 patients with MM at diagnosis, and 16 with pre viously treated MM. Results. In all the patients, the concentration of each angiogenic factor w as 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 a nd bFGF but this increase was not found in the other 6 patients with extram edullary disease when compared with patients without extramedullary disease . VEGF and bFGF did not correlate with each other white HGF showed a weak c orrelation with VEGF and a stronger one with bFGF. Moreover, VEGF correlate d with features of disease activity, such as C-reactive protein, and beta(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 ce lls. Since angiogenic factors may be released by normal cells in response t o hypoxia, we also evaluated erythropoietin (EPO) levels (which correlate w ith the hypoxic stimulus) both in PB and BM plasma of these patients but no ne 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 progr ession of disease may be different. The finding of higher levels of these f actors in BM than in PB might Indicate that the bone marrow environment is their major source. Concentrations of angiogenic factors parallel the activ ity of disease and are independent of the hypoxic stimulus. (C)2000, Ferrat a Storti Foundation.