ActD treatment induces cell death in human TP53^wt B-cell lymphomas. (A) ActD IC₅₀ values of a data set with 740 tumor cell lines from the Genomics of Drug Sensitivity in Cancer (GDSC) database ranked by sensitivity to ActD (left) and box plot showing IC₅₀ values of hematologic (blood-borne) and nonhematologic (others) tumors (right). Box plot represents median and first and third quartiles per group, with individual values for each cell line, and the mean IC₅₀ (+) is indicated. The mean IC₅₀ of ActD is 5.26 (95% confidence interval [CI], 2.96-7.56) in blood-borne tumor cell lines vs 74.12 (95% CI, 34.87-111.36) in other tumor type cell lines. ****P < .0001 (Mann-Whitney-Wilcoxon test). (B) Box plot showing IC₅₀ values of blood-borne tumors as a function of their TP53 status. Box plot represents median and first and third quartiles per group with individual values for each cell line, and the mean IC₅₀ (+) is indicated. ****P < .0001 (Mann-Whitney-Wilcoxon test). (C) Proportion of dead cells from a panel of wt TP53 (TP53^wt) and mutant TP53 (TP53^mut) BL- and DLBCL-derived cell lines (shown in boldface) determined by propidium iodide (PI) staining and flow cytometry analysis after treatment with 10 nM ActD for 48 hours (n = 3-4). Data are presented as mean ± SEM. ***P < .001; ****P < .0001 (2-way ANOVA test). (D) Scatter plot showing proportion of dead cells from panel C as a function of their TP53 status. Box plot represents median and first and third quartiles per group with individual values for each cell line, and the mean IC₅₀ value (+) is indicated. *P < .05 (Mann-Whitney-Wilcoxon test). (E) Representative western blot analysis from lysates of the panel analyzed in panel C treated with 10 nM ActD for the indicated times (n = 3-4). TP53^mut cell lines are shown in pink boldface. ALL, acute lymphoblastic leukemia; CLL, chronic lymphocytic leukemia; AML, acute myeloid leukemia; CML, chronic myeloid leukemia; MM, multiple myeloma; U, unclassified.