In vivo mouse leukemia models and patient-derived xenograft models of NUP98-fusion leukemia respond to menin-MLL1 inhibition. (A) Survival analysis of CD45.1 mice engrafted with NUP98-JARID1A mouse leukemia cells (CD45.2), treated with control or 0.1% VTP50469 chow (yellow shading) (n = 5 control mice, n = 8 VTP50469-treated mice). (B) Percent TdTomato positive CD45.2 positive NUP98-JARID1A mouse leukemia cells in the peripheral blood of CD45.1 recipient mice treated with control or 0.1% VTP50469 chow (n = 5 control mice, n = 8 VTP50469-treated mice). (C) Survival analysis of NOG mice engrafted with a NUP98-NSD1 PDX, treated with control, 0.05% or 0.1% VTP50469 chow (n = 5 mice per group; P < .001 using Log-rank [Mantel-Cox test]). (D) Percent human CD45 cells in the peripheral blood of NOG mice engrafted with a NUP98-NSD1 PDX, treated with control, 0.05% or 0.1% VTP50469 chow (n = 5 mice per group). Error bars represent S.E.M. (E) Survival analysis of NOG mice engrafted with a NUP98-JARID1A PDX, treated with 0.1% VTP50469 chow for 60 days (yellow shading) (n = 5 mice per group; P < .001 using Log-rank [Mantel-Cox test]). (F) Percent human CD45 cells in the peripheral blood of NOG mice engrafted with a NUP98-JARID1A PDX, treated with control or 0.1% VTP50469 chow for 60 days (yellow shading) (n = 5 mice per group). (G,H) Heatmap of gene expression changes characterized by RNAseq in human CD45 cells isolated from BM of NOG mice bearing a NUP98-NSD1 PDX (G) or NUP98-JARID1A PDX (H). Values in each cell represent the Log2 fold change in gene expression (VTP treated mice/Control mice).