[Wnt signaling in myeloma.]

Multiple myeloma(MM)develops and expands almost exclusively in the bone marrow, and generates devastating bone destruction. A variety of cytokines are overproduced in MM to stimulate RANKL-mediated osteoclastogenesis while suppressing osteoblastic differentiation from bone marrow stromal cells, leading to extensive bone destruction with rapid loss of bone. Soluble Wnt inhibitors elaborated from MM cells and/or their surrounding cells in bone lesions play an important role. Novel therapeutic neutralizing antibodies against DKK-1 or sclerotin are expected as bone anabolic agents;however, their effects on MM tumor progression through activation of the Wnt/β-catenin pathway remain to be carefully clarified.