BMSC-derived GDF15 enhances clonogenic MM growth. (A) Serial colony formation by NCI-H929 cells cocultured with MM BMSC in the presence or absence of anti-GDF15 antibody (Ab) for 4 days. *P < .05 compared with NCI-H929 cell only. (B) GDF15 secretion by primary BMSCs derived from HVs (light gray) and MM patients (dark gray) cultured alone or with NCI-H929 (H929), Granta519, Jeko-1, or normal CD138⁺ plasma cells. Cell culture inserts inhibited cell-cell contacts between NCI-H929 cells and MM BMSCs. *P < .05 compared with MM BMSC only. (C) Survival of Gdf15^null or wild-type (WT) mice after injection of Vk*Myc MM cells (n = 5 for each group). (D) Secondary transplantation of BM derived from mice initially engrafted with Vk*Myc MM cells.