Fig. 7: Inhibition of purine biosynthesis sensitizes MLLr AML cells to menin inhibitor.

a, b HSA synergy score of MMF plus VTP-50469 (a) and CX-5461 plus VTP-50469 (b) in MOLM-13 cells. A synergy score >10 represents a synergistic effect. c, d HSA synergy score of MMF plus VTP-50469 (c) and CX-5461 plus VTP-50469 (d) in MV4-11 cells. e, f HSA synergy score of MMF plus VTP-50469 (e) and CX-5461 plus VTP-50469 (f) in NB4 cells. g Kaplan-Meier analysis of survival of MLL-AF9-induced AML recipient mice treated with control or ziftomenib (25-100 mg/kg/day) (n = 8-9). h, i Frequency of GFP+ AML cells in PB (h) and survival analysis (i) of AML mice treated with control (n = 10), MMF (100 mg/kg/day) (n = 8), ziftomenib (12.5 mg/kg/day) (n = 10), or a combination of MMF and ziftomenib (n = 11 mice). j Schematic flowchart created with Biorender depicting the AML PDX study with MMF (100 mg/kg/day) and ziftomenib (12.5 mg/kg/day) treatments. k, l Frequency of hCD45+ AML cells in bone marrow of mice transplanted with AML001 (k) (Control n = 4, MMF n = 6, ziftomenib n = 5, and combination n = 5 mice) and AML013 PDX samples (l) (n = 5 mice per group). All data are represented as mean ± SD. p values in this figure were calculated by permutation tests (a–f) and ANOVA with multiple comparisons analysis using Bonferroni correction post hoc analyses (h, k, and l), or log-rank test (g and i). Source data are provided as a Source Data file.