Elevated level of plasma basic fibroblast growth factor in multiple myeloma correlates with increased disease activity.
Recent reports that bone marrow angiogenesis is increased in multiple myeloma prompted us to examine plasma concentrations of angiogenic growth factors and to elucidate their clinical and biological significance. In 45 cases including 36 cases of multiple myeloma and 9 cases of monoclonal gammopathies of undetermined significance (MGUS), plasma concentrations of basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF) were evaluated. FGF-2 was significantly elevated in 25 out of 45 (56%) of the patients with multiple myeloma compared with control subjects (median 9.01 pg ml vs. 1.58 pg/ml, P < 0.0001). The 25 cases were all active multiple myeloma, and none of the non-active myeloma and MGUS patients showed a high FGF-2 level. VEGF level was also elevated in 26 out of 45 patients (58%) compared with control subjects (median 42.0 pg/ml vs. 15.8 pg/ml, P < 0.0001 for VEGF). VEGF concentration was high in 20 active myelomas, but also in one non-active myeloma and five MGUS. Elevation of FGF-2 level was associated with beta2-microglobulin level, anemia and bone marrow plasma cell percentage, which represent disease activity. Interestingly, none of five Bence-Jones type myelomas, including four clinically active cases, revealed a high plasma FGF-2 level, while all of them showed a high VEGF level. In all five responders, the plasma FGF-2 levels were significantly decreased after chemotherapy. FGF-2 was immunohistochemically detected in the bone marrow myeloma cells of the patients with high plasma FGF-2 level. We conclude that plasma concentration of FGF-2 can be a useful indicator of disease activity.
Sato
Norihide
N
Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
Hattori
Yutaka
Y
Wenlin
Du
D
Yamada
Taketo
T
Kamata
Tamihiro
T
Kakimoto
Tsunayuki
T
Okamoto
Shinichiro
S
Kawamura
Chiharu
C
Kizaki
Masahiro
M
Shimada
Naoki
N
Ote
Yukiko
Y
Hata
Jun-ichi
J
Ikeda
Yasuo
Y
D000368:Aged; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003470:Culture Media / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000378:metabolism; D009389:Neovascularization, Pathologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000378:metabolism
D003470:Culture Media; D017077:Culture Media, Conditioned; D042461:Vascular Endothelial Growth Factor A; D001613:beta 2-Microglobulin; D016222:Fibroblast Growth Factor 2