Figure 4.
β2-selective inhibitor sensitizes hematological malignancies to immunoproteasome-selective inhibitors. (A) Comparison of IC50 values of LU102 determined 48 h after the continuous treatment in various hematological malignancies, data represent geometric mean ± geometric SD. Statistical significance was obtained with ANOVA and Tukey’s multiple comparison test. (B) Comparison of IC50 values of LU035i combined with fixed dose of LU102 (2.5 µM) determined 48 h after the continuous treatment in various hematological malignancies. Data represent geometric mean ± geometric SD. Statistical significance was obtained with ANOVA and Tukey’s multiple comparison test. (C) Paired comparison of IC50 values of LU035i combined with fixed dose of LU102 (2.5 µM) determined 48 h after the continuous treatment in AML samples. Statistical significance was obtained with paired t-test, where *** represents p < 0.001. (D) Paired comparison of IC50 values of LU035i combined with fixed dose of LU102 (2.5 µM) determined 48 h after the continuous treatment in B-ALL samples. Statistical significance was obtained with paired t-test, where * represents p < 0.05. (E) Paired comparison of IC50 values of LU035i combined with fixed dose of LU102 (2.5 µM) determined 48 h after the continuous treatment in MM samples. Statistical significance was obtained with paired t-test, where ** represents p < 0.01. (F) Paired comparison of IC50 values of LU035i combined with fixed dose of LU102 (2.5 µM) determined 48 h after the continuous treatment in MM samples. Statistical significance was obtained with paired t-test, where * represents p < 0.05. (G) Dose-response curves of AMO-1 wt and AMO-1 PSMB5 knock-out cells to LU102 determined 48 h after the treatment. Data represent mean ± SD. (H) Dose-response curves of AMO-1 cells to LU035i alone or in combinations with 2.5 µM LU102, determined 48 h after the treatment. Data represent mean ± SD. AML = acute myeloid leukemia, B-ALL = B-cell acute lymphoblastic leukemia, B-CLL = B-cell chronic lymphocytic leukemia, MM = multiple myeloma, PCL = plasma-cell leukemia, PBMC = peripheral blood mononuclear cells; LU035i = proteasome β5i selective inhibitor; LU102 = proteasome β2c and β2i selective inhibitor; i = immunoproteasome, c = constitutive proteasome.
