Fig. 4: The combination of VEN and AMG176 induces similar cell death and stress patterns in TP53-WT, -KO, and -mutant AML cells.

A TP53-WT, -KO, and -mutant (R175H and R248Q) Molm13 cells were treated with DMSO control, VEN, AMG176, or VEN plus AMG176, stained with an array of antibodies, and subjected to flow cytometry. Cells were then subjected to UMAP dimension reduction and projected on two-dimensional plots. The FlowSOM algorithm was utilized for automated cell population identification; the colors indicate FlowSOM clusters. B The UMAP plots for the indicated markers; the colors indicate marker expression intensity. C Heatmap of the arcsine-transformed expression intensities of the markers used for dimension reduction and clustering across the FlowSOM clusters shown in panel B. Live and dead cell clusters were identified based on the marker expression patterns shown in panel B. D Bubble plot of the frequencies of the FlowSOM clusters shown in panel A across TP53-WT, -KO, and -mutant (R175H and R248Q) Molm13 cells treated with control, VEN, AMG176, or VEN plus AMG176. E UMAP plot of the differential responses to treatment with control, VEN, AMG176, or VEN plus AMG176. The FlowSOM cluster frequencies shown in panel C were used for dimension reduction. F UMAP map of live cells (purple) and dead cells (gray) and heatmap of the expressions of the selected markers. G Violin plot of scaled Ki-67 signal intensities of TP53-WT, KO, and mutant leukemia cells and cells exposed to VEN, AMG176, or VEN plus AMG176 for 48 h. Live cells were selected for plotting and 200 cells (50 cells each of TP53-WT, KO, R175H, and R248Q) from each condition (control, AMG176, VEN, and combo) were shown. Cl cleaved, combo combination.