PU-H71 has antileukemia activity in NSG mice bearing TP53-mutant AML xenografts with minimal toxicity in normal hematopoiesis. NSG mice bearing TP53-R248W Molm13 cells received 30 or 50 mg/kg PU-H71, and leukemia-free NSG mice received 50 mg/kg PU-H71. (A) Disease progression and treatment responses in NSG mice bearing TP53-R248W Molm13 cells were assessed via in vivo luciferase imaging; (left) imaging of individual mice and (right) quantification of luciferase imaging of all mice per group. (B) Survival of NSG mice bearing TP53-R248W Molm13 cells were either vehicle- or PU-H71–treated. Arrows indicate treatment times. (C) RBC counts, WBC counts, and hemoglobin levels in leukemia-free NSG mice treated with 50 mg/kg PU-H71. Shaded areas indicate the treatment period. (D) Measurement of the epichaperome in healthy BM cells and Lin^–Sca1⁺c-Kit⁺ BM cells collected from leukemia-free NSG mice. RBC, red blood cell; WBC, white blood cell.