Targeting the interplay between myeloma cells and the bone marrow microenvironment in myeloma.

Cellular interplay in the bone marrow (BM) microenvironment in multiple myeloma (MM) mediates MM growth and the formation of bone-destructive lesions. MM cells show enhanced osteoclastogenesis, and stimulate angiogenesis in concert with BM stromal cells and osteoclasts, whereas they suppress osteoblastic differentiation, leading to devastating bone destruction and the rapid loss of bone. Importantly, osteoclasts, vascular endothelial cells, and BM stromal cells with defective osteoblastic differentiation create a cellular microenvironment suitable for MM growth and survival and confer a drug resistance to MM cells, which can be construed as the "MM niche". Therefore, the MM niche must be targeted and disrupted to improve the efficacy of anti-tumor treatment and prevent the progression of bone disease in MM. Clarifying molecular mechanisms leading to the formation of the MM niche along with bone disease will help in the development of novel approaches targeting the interplay between MM cells and the BM microenvironment.