BM stromal cells of precursor stages of MM disease are more prone to differentiate into adipocytes and increase the proliferation of myeloma cells. (A) Representative fluorescence-activated cell-sorting plots of BMSCs from HD and patients with MGUS/SMM and NDMM showing increased expression of adipogenic lineage markers at baseline. (B) Quantification of panel A. (C) Representative Oil Red O staining (C) and associated quantification of neutral lipids (D) from BMSC-derived adipocytes from HD and patients with MGUS/SMM and NDMM cocultured in the presence or absence of MM.1S cells in direct contact or in transwells. (E) Proliferation of MM.1S cells cocultured in the presence of pre-adipogenic BMSCs from HD and patients with MGUS/SMM and NDMM. (F) Proliferation of MM.1S cells cocultured with mature adipocytes differentiated from BMSCs from HD and patients with MGUS/SMM and NDMM. (G) Relative proliferation of 5TGM1 cells after 72 hours of coculture with MC3T3-E1 pre-osteoblasts or OP9 pre-adipocytes. Biospecimens from MGUS and SMM from MGUS and SMM patients were analyzed independently but were pooled together for analysis purposes. All data indicate n ≥ 3; mean ± standard error of the mean. *P < .05.