Fig. 2: The level of Bcl-2 expression determines venetoclax sensitivity of DLBCL cell lines in vitro and in vivo. | Leukemia

Fig. 2: The level of Bcl-2 expression determines venetoclax sensitivity of DLBCL cell lines in vitro and in vivo.

From: Inhibitors of Bcl-2 and Bruton’s tyrosine kinase synergize to abrogate diffuse large B-cell lymphoma growth in vitro and in orthotopic xenotransplantation models

Fig. 2

a Bcl-2 expression of the indicated cell lines as determined by Western blotting; tubulin expression served as loading control. The mutational status of the indicated genes is annotated below the western blots; the color code indicates the BCL2 status (yellow: BCL2 translocation; red: BCL2 amplification; black: wild-type BCL2). b Inverse correlation of Bcl-2 expression with the viability after BCL2 gene editing (upper panel) and venetoclax exposure (lower panel), of the indicated cell lines. The p values were determined by log-rank test. c BCL2 gene expression of 206 DLBCL cases available through TCGA, stratified based on genetic subtype as assigned by Schmitz et al. [10]. The p value was determined by Kruskal–Wallis test, and pairwise p values by Mann–Whitney–Wilcoxon test. Symbols indicate the subtype based on gene expression signature. d Apoptosis rates as determined by annexin V staining, of the indicated cell lines exposed to 40 nM venetoclax and/or the pan-caspase inhibitor z-VAD-FMK. Data are presented as mean ± standard deviation of three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.005, ****p < 0.001, as determined by one-way ANOVA. e–g MISTRG (RIVA, U2932) and MISTRG6 (HBL-1) mice were injected intravenously with 1 × 107 cells of the three indicated cell lines; IVIS images were recorded on the indicated days (e) and the radiance was plotted longitudinally as means ± SD (f). Mice received twice-weekly doses of 40 mg/kg venetoclax via oral gavage, initiated once lymphomas were clearly detectable in all mice of the cohort (after two and three weeks of growth, respectively; indicated by gray shading in f). The lymphoma burden was quantified in the bone marrow at the study endpoint by flow cytometric staining for human (hCD45) and mouse CD45 (4–5 weeks post injection, in g). Data are representative of at least two independent experiments; only one study was conducted with HBL-1 cells. Horizontal lines indicate medians. **p < 0.01, as determined by Mann–Whitney test. ns, not significant.

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