The Role of Cytokines, Growth and Angiogenic Factors in Patients with NEWLY Diagnosed Multiple Myeloma

Abstract 4997

The cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-a may play some roles in both the pathogenesis of multiple myeloma (MM) and bone destruction. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and angiopoietin (Ang)-2 in recent years may trigger angiogenesis in MM. Moreover transforming growth factor (TGF)-β and insulin-like growth factor (IGF)-1 induce angiogenesis and proliferation of myeloma cells. In this prospective study, we investigated the role of cytokines, growth and angiogenic factors in patients with newly diagnosed MM. Fifty patients (32 were male and 18 female, with mean age of 63 ± 11 years) with newly diagnosed MM were enrolled to this study. Local ethical commity of our university approved this study. 30 healthy individuals (12 were male and 8 female, with mean age of 55±9 years) were selected as control group. The exclusion criteria were malignancy, acute and chronic infections, autoimmune disorders, diabetes mellitus, immune deficiency, and chronic inflammatory diseases. According to Durie-Salmon staging system, 10%, 22%, and 68% of the patients with MM were in Stage I, Stage II and Stage III, respectively. 17%, 44%, and 39% of patients with MM were in International prognostic index-1 (IPI1), IPI2, and IPI3, respectively. 90% of the patients were symptomatic MM, 6% of them were smoldering MM, and solitary plasmacytoma was detected in 4% of the patients. The levels of IL-1β, IL-2, IL-6, IL15, TNF-a, VEGF, bFGF, TGF-β, HGF, IGF-1, Ang-1 and Ang-2 were determined using ELISA in patients and controls. VEGF and nuclear factor kappa-B (NFkB) were evaluated as immunohistochemistry in bone marrow biopsy in patients and pathological control group (13 were male and 6 female, with mean age of 64±14 years) with non-Hodgkin's lymphoma and without bone marrow involvement. In this study, the levels of IL-1β (p<0. 001), IL-2 (p<0. 001), IL-6 (p<0. 001), TNF-a (p<0. 001), IGF-1 (p<0. 001), TGF-β (p<0. 001), HGF (p=0. 004), and Ang-2 (p<0. 001) in patients were higher than controls. But there was no difference for Ang-1, IL-15, and VEGF in between two groups (p>0. 05). According to immunohistochemistry scoring, while NFkB scores in patients were higher than controls (p=0. 035), any significance was not detected for VEGF in between patient and pathological control groups (p>0. 05). According to Durie-Salmon staging system, TNF-a levels in Stage I were higher than Stage III (p=0. 035). According to IPI, TGF-β levels in patients with IPI-1 were higher than the patients with IPI-2 (p=0. 017) and IPI-3 (p=0. 003). The pathogenesis of MM is stil unclear. In this study, although VEGF did not increase, increment in the levels of Ang-2 and other growth factors indicated the induction of angiogenesis in MM. In earlier stage, this condition may be apparent.