Extended Data Fig. 2: Development of Menin-inhibitor resistance in a KMT2Ar PDX.
From: MEN1 mutations mediate clinical resistance to menin inhibition
a) Box-plot (median, box: 25th to 75th percentile, whiskers: range) showing the percentage (%) of human leukemia cells in the bone marrow of NOG-mice transplanted with PDX3 at baseline (n = 4), 4 weeks (w) (n = 4), 8w (n = 5) and at 10–12w (n = 5; symptomatic leukemia relapse) on Menin-inhibitor treatment. Dots represent individual animals. One-way ANOVA with correction for multiple comparisons was used for statistical analysis. b) Box-plots (median, box: 25th to 75th percentile, whiskers: range) showing the mean fluorescence intensity (MFI) of the myeloid differentiation markers CD11b, CD13 and CD14 on the cell surface of human cells detected in the bone marrow of NOG-mice transplanted with PDX3 at baseline (n = 4), 4w (n = 5), 8w (n = 4) and at 10–12w (n = 4) on Menin-inhibitor treatment. Dots represent individual animals. One-way ANOVA with correction for multiple comparisons was used for statistical analysis. c) Bone marrow cytology pictures (cytospins) from each 2 representative animals at baseline, 4w, 8w and 12w on Menin-inhibitor treatment. d) Pie charts showing the fraction of MEN1-T349M (red) as compared to MEN1-WT (blue) measured by droplet digital PCR (ddPCR) at baseline, 8 weeks and 12 weeks (fulminant clinical relapse) in human cells isolated from PDX3 mice and purified using magnetic cell sorting.
