RSK2 inhibition synergizes with lenalidomide to overcome BMSC-mediated drug resistance and it also enhances MM cytotoxicity mediated by other anti-myeloma drugs. (A) Myeloma cells (top panel, MM1.S cells; middle panel, XG1 cells) were incubated with indicated doses of drugs in the absence (left) or presence (right) of BMSCs. BMSCs were seeded at 5000/well in 96-well plates overnight before adding myeloma cells and indicated doses of drugs. MTT assays were read at day 5 after treatment. (B) JJN3 HMCLs were treated with indicated doses of BI-D1870, bortezomib (middle), dexamethasone (left), and melphalan (right) for 3 days, followed by MTT assay to measure cell viability.