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-α (TNF-α) 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-α 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-α. MVD values and serum levels of HGF and TNF-α were elevated in newly diagnosed MM patients in comparison with healthy controls. Pre-treatment MVD, HGF and TNF-α increased with advancing stage of MM disease. In patients reaching the plateau phase, a significant reduction in MVD, HGF and TNF-α levels occurred. A positive correlation was noted between pre-treatment MVD and serum levels of TNF-α and lactic dehydrogenase but not with HGF. However, HGF strongly correlated with β₂-microglobulin (β₂M), TNF-α 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-α, increases with advancing clinical stage and decreases after effective chemotherapy.