Treatment with FHD-286 concordantly alters chromatin accessibility and mRNA expression in MLL1-rearranged AML cells with reduction in the enrichment scores for MYC, mTORC1, E2F, interferon gamma, IL6-JAK-STAT3, as well as of inflammatory response and oxidative phosphorylation gene sets. (A-B) MOLM13 cells were treated with 100 nM of FHD-286 for 16 hours as biologic replicates. Bulk nuclei were isolated for ATAC-Seq analysis and total RNA was isolated and used for RNA-Seq analysis. RNAs and diffReps-determined ATAC-Seq peaks with ≥1.25-fold change and P value <.05 were used for the concordance analysis. Circos plot (A) and log2 fold-changes (B) of selected, concordant ATAC-Seq, and mRNA expression alterations in FHD-286–treated MOLM13 cells. (C) Gene set enrichment analysis of FHD-286–treated MOLM13 cells compared with HALLMARK pathways. Normalized enrichment scores are shown. All q-values are <0.1. (D) Enrichment plot of FHD-286–treated MOLM13 cells compared with HALLMARK_MYC_TARGETS_V1 and HALLMARK_MYC_TARGETS_V2. (E) Volcano plot (log2 fold change vs −log10 P value) of RNA-Seq determined mRNA expression changes in FHD-286–treated MOLM13 cells.