Angiogenesis is a constant hallmark of multiple myeloma (MM) progression and has
prognostic potential. It is induced by plasma cells via angiogenic factors with the transition from
monoclonal gammopathy of undetermined significance (MGUS) to MM, and probably with loss of
angiostatic activity on the part of MGUS. Soluble angiogenic factors are elevated in the bone marrow
and peripheral blood samples form MM patients. The pathophysiology of MM-induced angiogenesis
involves both direct production of angiogenic cytokines by plasma cells and their induction within the
bone marrow microenvironment cells. The latter are secreted by stromal cells and promote plasma cell
growth, survival and migration, as well as paracrine cytokine secretion and angiogenesis in the bone
marrow milieu. More recently, a direct involvement of bone marrow macrophages and mast cells in
vasculogenic mimicry has been demonstrated, thus contributing together with circulating endothelial
cells and endothelial precursor cells (EPCs) to the MM neovascularization. Finally, controversial data
are available concerning the correlation between angiogenesis and disease stage and prognosis.
Keywords: Angiogenesis, VEGF, FGF-2, HGF, Ang-1, Ang-2, IGF-1, IL-8, OPN, ADM, TNF, MMP-2/9,
CXCL8/IL8, CXCL11/I-TAC, CXCL12/ SDF-1, bone marrow endothelial cells, circulating endothelial
cells, endothelial precursor cells, macrophages, mast cells, vascular mimicry.
