title: Bone marrow microvascular density and angiogenic growth factors in multiple myeloma.
abstract: 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.
authors.affiliation: Department of Hematology, University Hospital of Heraklion, Crete, Greece. freda@med.uoc.gr
authors.forename: Michael G
authors.initials: MG
authors.lastname: Alexandrakis
authors.forename: Freda J
authors.initials: FJ
authors.lastname: Passam
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Ganotakis
authors.forename: Evgenios
authors.initials: E
authors.lastname: Dafnis
authors.forename: Constantina
authors.initials: C
authors.lastname: Dambaki
authors.forename: John
authors.initials: J
authors.lastname: Konsolas
authors.forename: Despina S
authors.initials: DS
authors.lastname: Kyriakou
authors.forename: Efstathios
authors.initials: E
authors.lastname: Stathopoulos
mesh_terms: 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
chemical_list: 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