MLL and menin are molecular dependencies in NUP98-rearranged leukemia. (A) NUP98-HOXA9 (top panel) and NUP98-JARID1A (bottom panel) mouse leukemia cells engineered to constitutively express Cas9 were transduced with sgRNA targeting MLL1, menin, RPA3 (positive control) and luciferase (negative control). Cells expressing sgRNA also express an RFP or GFP reporter, and the y-axis quantifies the percent RFP+ or GFP+ cells at each time point. Bars represent mean ± SEM. Two-way ANOVA with Dunnett’s multiple comparisons test was performed, ****P < .0001. Data are representative of 3 independent experiments. (B,C) Mouse leukemia cells expressing NUP98-HOXA9 (B) or NUP98-JARID1A (C) were treated with an escalating dose curve of VTP50469. Data are representative of 5 independent experiments. (D,E) Expression of CD11b on NUP98-HOXA9 (D) or NUP98-JARID1A (E) mouse leukemia cells treated with an escalating dose curve of VTP50469. Data are representative of 5 independent experiments. Bars represent mean ± SEM. Two-way ANOVA with Dunnett’s multiple comparisons test was performed, ***P = .002, ****P < .0001.