Cooperating alterations and differentiation status affect sensitivity to menin inhibition. (A) Experimental schema showing revumenib treatment. (B) Relative cell growth of cbCD34 NUP98::KDM5A models with gRNA treated with revumenib (0.1-1 μM) compared with dimethyl sulfoxide controls. (C) Flow gating (top), CD34⁺CD41a⁺ population (left), CD34^–CD41a⁺ population (middle), and CD34^–CD11B⁺ populations (right) among mCherry⁺ GFP⁺ mAmetrine⁺ live population at day 15. (D) GSEA analyses between dimethyl sulfoxide and revumenib-treated conditions, colors showing NES (top-left), comparison of expression changes between AAVS and RB1-gRNA1 conditions (right), and gene ontology term analysis of changes enriched (difference of fold changes >1) in AAVS conditions (bottom-left). (E) Relative cell growth of unedited cbCD34 NUP98::KDM5A (control, black), CHRF-288-11 (red), and ST1653 patient-derived xenograft (blue) treated with revumenib (0.1-1 μM) compared with dimethyl sulfoxide controls. (F) Schematics illustrating a cellular hierarchy of NUP98::KDM5A models created in BioRender. Umeda, M. (2025) https://BioRender.com/kreq8kl. Data were obtained from 3 technical replicates using gRNA-transduced cells in Figure 6. One data point at day 15 was excluded for technical errors. Statistical tests were performed by a generalized linear mixed effect model with Gaussian distribution, followed by the Benjamini-Hochberg adjustment (B,E) or Student t test by comparing gRNA conditions with AAVS controls (C). Asterisks indicate P values or adjusted P values; ∗P < .05. Error bars indicate mean ± standard error of the mean. DMSO, dimethyl sulfoxide; NES, normalized enrichment score.