Proteasome inhibitors downregulate TRAIL expression in leukemic LGLs. (A-C) TL-1 (A), NKL (B), and LGL PBMCs (C; T-LGL n = 7, NK-LGL n = 3) were treated with bortezomib, ixazomib, or DMSO vehicle for 6 hours. Relative TRAIL mRNA expression was determined by quantitative real-time PCR. Values are presented as mean ± SEM. *P < .05 indicates significant difference between DMSO and proteasome inhibitor treatments (Student t test). In panel C, **P = 1.84E−5 and ***P = .0015. (D-F) LGL leukemia cell line TL-1 (D), NKL (E), or LGL patient PBMCs (F; T-LGL n = 4; NK-LGL n = 2) were treated with bortezomib (5 nM), ixazomib (100 nM), or DMSO, and total protein samples were collected to assess TRAIL protein levels by immunoblotting assay. Equal loading for western blot assay was confirmed by probing with β-actin antibody. Vertical lines within some patient blots indicate regions where lanes were removed from the image in order to show identical time points for all samples.