NSC12 leads to enhanced anti-WM activity when used in combination with PIs. (A-C) BCWM.1 and MWCL.1 cells were exposed to NSC12 (6 μM) for 12 hours and subjected to wide transcriptome profiling, showing a significant inhibition of antigen processing ubiquitination proteasome degradation- (A), ER stress- (B), and UPR (C) -related gene sets, as shown by performing GSEA (P < .05; FDR < 25%). (D) BCWM.1 and MWCL.1 cells were treated with NSC12 (0.3 to 3 μM) or bortezomib (2.5 to 5 nM) as single agents, or the combination. Modulation of cell survival at 48 hours was tested on WM cells using MTS assay. Average of triplicate experiments ± SD is shown. P, P value.