MLL1 is displaced from chromatin upon treatment with VTP50469 at a subset of critical genes. (A,B) Gene expression changes at day 3 (top panels) and day 6 (bottom panels) of treatment with 2 μM VTP50469 in mouse leukemia cells expressing NUP98-HOXA9 (A) or NUP98-JARID1A (B). n = 3 replicates per time point. (C,D) Gene-set enrichment analysis of gene expression changes in NUP98-HOXA9 (C) or NUP98-JARID1A (D) mouse leukemia cells treated with VTP50469 compared with that seen in MLL-r (MA9) and NPM1c mouse leukemia cells. (E) Tornado plots and average signal plots depicting genome-wide MLL1, menin, and H3K4me3 chromatin changes upon treatment with VTP50469 as determined by ChIPseq in mouse leukemia cells expressing NUP98-HOXA9. (F) Gene tracks of MLL1 chromatin occupancy in NUP98-HOXA9 mouse leukemia cells treated with VTP50469 as determined by ChIPseq in reads per million (rpm) at selected genes. (G) Violin plots depicting change in MLL1 occupancy for genes that display changes in gene expression vs all genes in NUP98-HOXA9 mouse leukemia cells after 3 days (left panel) or 6 days (right panel) of treatment with VTP50469. Data are representative of 2 independent experiments. One-way ANOVA was performed.