Multiple Myeloma Bone Marrow Angiogenesis

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.