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. 2023 Feb 25;23:36. doi: 10.1186/s12935-023-02877-y

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© The Author(s) 2023

Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 4 — The Menin-MLL1 inhibitor induced gene expression changes through Menin-MLL1 chromatin-associated complexes. A RNA-seq was performed in MOLM-13 and NCCHD010 cells treated with DS-1594a·succinate for 3 and 7 days, respectively. GSEA of MOLM-13 cells treated with 100 nM DS-1594a·succinate for 3 days and NCCHD010 cells treated with 500 nM DS-1594a·succinate for 7 days. B RT‒qPCR was performed in MOLM-13 and NCCHD010 cells treated with DS-1594a·succinate for 3 and 7 days, respectively, at the indicated concentrations. The graphs represent the expression levels of the indicated genes compared to those in the DMSO-treated control (mean ± SD, n = 3). C Changes in Menin/MLL1 occupancies in MOLM-13 and NCCHD010 cells treated with 100 nM or 5 μM DS-1594a·HCl or DS-1594a·succinate, respectively, for 3 days. Normalized coverage tracks of Menin, MLL1, H3K79me2, and H3K4me3 ChIP-seq signals (reads per million) at selected target genes in MOLM-13 or NCCHD010 cells are shown. The peaks around the TSS are shown. D Analysis of the leukemic stem cell score. LSC17 scores and pLSC6 scores in AML676 and NCCHD010 cells were calculated for each sample treated with DMSO or DS-1594a·succinate at the indicated concentrations (n = 3). The numbers on the plots are P values of the Jonckheere-Terpstra trend test with Bonferroni correction. For the GSEA, the t test results were used as the metrics for scoring and ranking genes. The FDR q value for each gene set was calculated with the permutation of the gene sets. LSC17, 17-gene adult LSC; pLSC6, 6-gene pediatric LSC; TSS, transcription start site