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Angiogenic factors in multiple myeloma: higher levels in bone marrow than in peripheral blood
F Di Raimondo1, M P Azzaro, G Palumbo
1Divisione di Ematologia, Ospedale Ferrarotto, V. Citelli 6, 95124 Catania, Italy. diraimon@sirio-oncology.it
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.
Insights
Soluble angiogenic factors like VEGF, bFGF, and HGF are elevated in multiple myeloma (MM) bone marrow compared to peripheral blood. Their levels correlate with disease activity but not hypoxia, suggesting the bone marrow microenvironment is a key source.
Area of Science:
- Oncology
- Molecular Biology
- Hematology
Background:
- Multiple myeloma (MM) is characterized by angiogenesis, a process involving the formation of new blood vessels.
- Soluble angiogenic factors are implicated in tumor growth and progression.
Purpose of the Study:
- To investigate the role of specific soluble angiogenic factors in the angiogenesis associated with multiple myeloma.
- To compare the levels of these factors in bone marrow and peripheral blood.
Main Methods:
- Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF) concentrations were measured using ELISA.
- Plasma samples were collected from peripheral blood and bone marrow aspirates of 34 patients with plasma cell disorders, including MM.
Main Results:
- All three angiogenic factors showed higher concentrations in bone marrow (BM) compared to peripheral blood (PB).
- Factor levels were lower in early-stage (Stage I) MM patients than in advanced stages (Stage II-III).
- VEGF correlated with disease activity markers (C-reactive protein, β2-microglobulin), while bFGF and HGF inversely correlated with albumin levels. No correlation was found with hypoxia (EPO levels).
Conclusions:
- Soluble angiogenic factors play a role in MM, with potentially different contributions to disease progression.
- Elevated levels in BM suggest the bone marrow microenvironment is a primary source of these factors.
- Angiogenic factor concentrations reflect disease activity and are independent of hypoxic stimuli.