Fig. 7: Statins are inadequate to fully reverse AraC resistance in PDX models and a retrospective cohort of TP53^mut AML patients.

A Schema (created in BioRender) of TP53^mut AML PDX model. In brief, primary, human TP53^mut AML cells (chemoresistant SCXC-5052) were injected into the tail veins of busulfan-pretreated NSG mice. Engraftment was confirmed on bone marrow aspirates followed by initiation of treatment with vehicle, AraC (50 mg/kg/day IP for D1-5), rosuvastatin (1 mg/kg/day PO for D1-7) or the two drugs in combination. On D8 mice were humanely sacrificed and bilateral femurs/tibias and spleen were harvested (n = 7 mice per condition, early death of 3 mice in AraC condition). B Leukemic burden in millions of hCD45 + hCD33+ cells in the bone marrow and spleen combined for each mouse as quantified with counting beads by flow cytometry. C CoQ10 (ng) and D cholesterol (μg) per 0.5 million magnetic bead-purified hCD45+ leukemic cells from the bone marrow of mice with each circle representing the average of 1 mouse, as assessed by MS (5 replicates per mouse; n = 7, 4, 7, 7 mice for Control, AraC, Statin and AraC + Statin, respectively). E Basal and maximum coupler-induced oxygen consumption in pmol/minute assessed by Seahorse technology in magnetic bead-purified hCD45+ leukemic cells from the bone marrow with each circle representing the average of 1 mouse (n = 4, 3, 2, 2 mice for Control, AraC, Statin and AraC + Statin, respectively). F Kaplan–Meier survival estimates from a retrospective study of newly diagnosed TP53^mut AML patients (n = 364) who did or did not receive a concurrent statin during induction therapy (n = 115 and n = 249, respectively). Unless otherwise noted, statistical analysis by two-way ANOVA with FDR correction for multiple comparisons. Adjusted p-values: * = <0.05, ** = <0.01, *** = <0.001. n is the number of replicates. OCR oxygen consumption rate.