Concomitant PP2A activation and BCL2 inhibition significantly decreases the clonogenic potential and proliferation of primary AML cells ex vivo. (A) Bar graphs show the percentage of colonies grown after exposure to different treatments. Data were analyzed by one-way ANOVA and Tukey post hoc test analyses; ∗P < .05, ∗∗P < .01, ∗∗∗P < .001. (B) Heatmaps show the CI values of FTY720 plus venetoclax in 5 primary AML samples. (C) Representative images of colonies grown upon treatment exposure. Scale bars: 400 μM. Bar graphs show reduction of venetoclax (D) or A-1331852 (BCL-XL inhibitor) (E) IC50 values upon combination with FTY720 in 21 distinct primary AML samples at diagnosis. (F) Heatmap representations of viability percentages and CI values, along with cell viability curves of FTY720 combined with venetoclax at increasing concentrations in cells from patients with AML (AML-6, AML-7, and AML-11) (60 hours of treatment). (G) After combo treatment (36 hours), MCL1, Ser70p-BCL2, and Thr202/Tyr204p-ERK levels were significant decreased in therapy-responsive samples (AML-7 and AML-11). ANOVA, analysis of variance; ns, not statistically different.