Figure 3.

Cytotoxicity of subunit-selective proteasome inhibitors in BCP-ALL and T-ALL and correlation with immunoproteasome activity. (A) Comparison of the cytotoxicity of LU015i between BCP-ALL and T-ALL samples, p was obtained with Mann–Whitney U test. (B) Correlation between the ratio of activity of proteasome β5i versus β5c, determined by ABPs, and cytotoxicity of LU015i in BCP-ALL, expressed as individual IC₅₀ values. r and p were obtained with Spearman’s correlation. (C) IC₅₀ values of LU102 in T-ALL samples. (D) Paired comparison of IC₅₀ values of BTZ alone or combined with fixed dose of LU102 (1 µM) determined 48 h after the continuous treatment in T-ALL. p was obtained with Wilcoxon’s paired test. (E) Paired comparison of IC₅₀ values of IXZ alone or combined with fixed dose of LU102 (1 µM) determined 48 h after the continuous treatment in T-ALL. p was obtained with Wilcoxon’s paired test. (F) Cell viability (normalized to untreated control cells as 100%) in T-ALL after 48 h treatment with 1 µM LU015i alone or in combination with 1 µM LU102. p was obtained with Wilcoxon’s paired test. BTZ = bortezomib, IXZ = ixazomib, LU102 = a β2 selective inhibitor, LU015i = a β5i selective inhibitor, BCP-ALL = B-cell precursor acute lymphoblastic leukemia, T-ALL = T-lineage acute lymphoblastic leukemia, i = immunoproteasome, c = constitutive proteasome.