Knockdown or inhibition of RSK2 in myeloma cell lines induced apoptotic signaling and downregulation of IRF4, MYC, and MCL1. (A) Myeloma cell lines (MM1.S and H929) were infected with NT and RSK2 shRNAs lentivirus. After 48 hours, cells were harvested and used for immunoblotting assay to measure the expression of IRF4, MYC, MCL1, BIM, and PARP. (B) H929 cells were incubated with BI-D1870 (BI, 3 μM) at indicated time points, followed by immunoblotting analysis. (C) JJN3 cells were incubated with BI-D1870 at indicated doses for 6 hours, followed by immunoblotting analysis. (D) JJN3 cells were incubated with 2 μM of BI-D1870 for 3 hours, followed by qPCR analysis of MYC and IRF4 expression at transcription level.