Bone marrow microvascular density and angiogenic growth factors in multiple myeloma.
There is evidence that angiogenesis plays an important role in the progression of multiple myeloma (MM). Hepatocyte growth factor (HGF) and tumor necrosis factor-alpha (TNF-alpha) are cytokines that potently stimulate angiogenesis. We evaluated the microvascular density (MVD) of bone marrow biopsies (after immunostaining with anti-CD34 antibodies) and serum levels of HGF and TNF-alpha in 43 patients with newly diagnosed MM. Twenty-four of these patients reached a plateau phase after treatment and were reevaluated for MVD, HGF and TNF-alpha. MVD values and serum levels of HGF and TNF-alpha were elevated in newly diagnosed MM patients in comparison with healthy controls. Pre-treatment MVD, HGF and TNF-alpha increased with advancing stage of MM disease. In patients reaching the plateau phase, a significant reduction in MVD, HGF and TNF-alpha levels occurred. A positive correlation was noted between pre-treatment MVD and serum levels of TNF-alpha and lactic dehydrogenase but not with HGF. However, HGF strongly correlated with beta2-microglobulin (beta2M), TNF-alpha and lactate dehydrogenase (LDH). We conclude that angiogenesis in MM, as expressed by the bone marrow MVD and the serum levels of angiogenic molecules such as HGF and TNF-alpha, increases with advancing clinical stage and decreases after effective chemotherapy.
Alexandrakis
Michael G
MG
Department of Hematology, University Hospital of Heraklion, Crete, Greece. freda@med.uoc.gr
Passam
Freda J
FJ
Ganotakis
Emmanuel
E
Dafnis
Evgenios
E
Dambaki
Constantina
C
Konsolas
John
J
Kyriakou
Despina S
DS
Stathopoulos
Efstathios
E
D000328:Adult; D000368:Aged; D042501:Angiogenic Proteins / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D001853:Bone Marrow / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000098:blood supply* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000097:blood / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000097:blood / Q000378:metabolism
D042501:Angiogenic Proteins; D014408:Biomarkers, Tumor; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D042442:Vascular Endothelial Growth Factors; D001613:beta 2-Microglobulin; D017228:Hepatocyte Growth Factor; D007770:L-Lactate Dehydrogenase