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. 2023 Apr 8;14:1979. doi: 10.1038/s41467-023-37712-5

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 8 — a Effects on the proliferation of P31/FUJ cells by dual inhibition of MOZ/MORF KATs and DOT1L KMT. Proliferation of P31/FUJ cells in the presence of WM1119 and EPZ-5676 at the indicated concentrations was monitored for 21 days. b Differentiation of P31/FUJ cells after combinatorial inhibition of MOZ/MORF KAT and DOT1L KMT. Flow cytometry analysis for the CD11b antigen was performed on the P31/FUJ cells treated with various combinations of WM1119 and EPZ-5676 for 6 days. c Effects of combinatorial inhibition of MOZ/MORF KAT and DOT1L KMT on gene expression. RT-qPCR was performed on the P31/FUJ cells treated with only 100 nM WM1119 (WM), only 1 µM EPZ-5676 (EP), or a combination of both (WM & EP) (mean of two technical replicates). d Effects on the colony formation of human CD34 + cells and P31/FUJ cells by dual inhibition of MOZ/MORF KATs and DOT1L KMT (mean ± SD of technical replicates, n = 3). e Effects on the cell numbers of Human CD34 + cells and P31/FUJ cells by dual inhibition of MOZ/MORF KATs and DOT1L KMT (mean ± SD of three technical replicates). f Leukemia burden before and after the combination therapy using MOZ/MORF KATs and DOT1L KMT inhibitors. P31/FUJ human leukemia cells expressing LUC2Red were transplanted into sublethally irradiated SCID mice and subsequently administered with 35 mg/kg of WM119 and 20 mg/kg of EPZ-5676 three times a day (i.p.) for 2 weeks (mean ± SD of biological replicates, n ≥ 9). Welch’s t-test (two-sided) was performed on the indicated two-group comparison. Survival of transplanted recipient mice with or without MOZ/MORF KAT inhibitor treatment (the duration of drug administration is indicated in the graph). A log-rank (Mantel–Cox) test was performed. n.s.: P > 0.05. Source data are provided as a Source Data file.