PU and VEN combination synergistically targets AML cells and stem/progenitor cells with TP53 mutations but with limited activities against healthy BM and BM stem/progenitor cells. PB cells from patients with primary AML with TP53 mutations and healthy BM cells were treated with PU, VEN, or both. (A-B) Cell death of AML cells and stem/progenitor cells at 48 hours treatments (A) and clonogenic assay (B) in primary samples from patients. (C) Viable cells in Ki-67–low (solid markers) and –high (open markers) AML cells and stem/progenitor cells from patients with TP53 mutations. (Left) Ki-67 staining of 1 of the samples. (Middle and right) Viable CD45⁺ cells or CD34⁺CD38^– cells in various treatment groups compared with the untreated control. Patient samples used for various treatments and patient characteristics are shown in supplemental Table 1. (D-E) Cell death at 48-hour treatments (D) and clonogenic assays (E) in healthy BM samples. Primary cells were cocultured with MSCs during treatments. For colony assays, error bars represent mean ± SEM of 3 plating × 2 counting of each sample. ∗P ≤ .05; ∗∗P ≤ .01; ∗∗∗P ≤ .001; ∗∗∗∗P ≤ .0001. BFU-E, burst forming unit-erythroid.