PU plus VEN has enhanced antileukemia activity against both TP53-WT and -mutant AML in vivo. NSG mice injected with a mixture of luciferase-/GFP-labeled TP53-WT Molm13 cells and BFP-labeled TP53-R248W Molm13 cells (10:1 ratio) or NSGS mice injected with a PDX TP53-mutant cells (2 × 106 cells per mouse) were treated with PU (50 mg/kg), VEN (50 mg/kg), or both. (A) Luciferase imaging of leukemia burden in NSG mice: (left) images of individual mice and (right) quantification of luciferase imaging of all mice per treatment group). (B) Flow cytometry was used to identify TP53-WT and -R248W Molm13 cells in PB and BM after 3-week treatment. (C) Circulating blasts and spleen weight after 4-week treatment (left) and mouse survival in NSGS mice (right). PDX, patient-derived xenograft.
