“…Released cytokines, chemokines and growth factors from myeloma cells interact with the microenvironment, causing auto-crine and paracrine secretion of insulin-like growth factor 1, interleukin-6 (IL-6), fibroblast growth factor receptor 3 (FGFR3), vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α) and transforming growth factor-ÎČ [24]. The bone marrow microenvironment comprises several cell types such as hematopoietic cells, stromal cells, fibroblasts, bone marrow stromal cells (BMSCs), osteoblasts, osteoclasts, endothelial cells and immune cells, as well as noncellular components that include extracellular matrix, cytokines, growth factors and chemokines [23]. The onset of MM is due to the accumulation of abnormal plasma cells in the bone marrow that adhere to extracellular matrix and BMSCs, which play a key role in the pathogenesis of MM [25].…”