Proteasome inhibitors induce apoptosis in LGL leukemia samples. (A) PBMCs from normal donors (n = 9), T-LGL patients (n = 16), and NK-LGL patients (n = 6) were treated with DMSO or bortezomib (2.5 or 5 nM) for 48 hours, and cells were stained for apoptosis with Annexin-V and 7-AAD and analyzed by flow cytometry (left). PBMCs from normal donors (n = 9), T-LGL patients (n = 12), and NK-LGL patients (n = 6) were treated with DMSO or ixazomib (100 or 200 nM) for 48 hours, and cells were stained for apoptosis with Annexin-V and 7-AAD and analyzed by flow cytometry (right). (B) PBMCs from patients with T-LGL leukemia were treated with proteasome inhibitor bortezomib (5 nM) or ixazomib (100 nM) for 24 hours, and c-FLIP, caspase-3, and PARP cleavage was determined by western blot assay. Equal loading for all western blot assays was confirmed by probing with a β-actin antibody. (C) PBMCs from normal donors (n = 3) and T-LGL patients (n = 4) were treated with DMSO, bortezomib, or ixazomib for 48 hours. Cells were stained for CD3, CD8, CD57 and apoptosis markers. *P < .05, **P < .01, ***P < .001 (1-way ANOVA) significant differences between T-LGL patients and normal donors.