Myeloma cells treated with its inhibitor, APO866, undergo apoptosis.229 In contrast, downregulation of adiponectin is detrimental in SMM and MM,230 as adiponectin prevents disease progression by activating p21 and p53 or activating AMPK and MAPK signaling to induce cell cycle arrest and apoptosis in myeloma cells.231 As bone resorption and formation may yield differential gradients of leptin and adiponectin levels (Fig. 4.3), the distinct stage of bone remodeling likely impacts MM cells through adipokine-mediated pathways. This evidence concerns the gene ADIPOQ and plasma cell myeloma.