p300i is invariably effective during early stages of resistance to BET inhibition. (A) Graphical schema of the experimental approach to induce and store cells at all stages of resistance to BETi in SKNO1 and OCI-AML3 cells. (B) Experimental approach to the assessment of transcriptional changes via RNA-Seq during the longitudinal scale of establishment of resistance to BETi. To avoid putative sequencing-related batch effects, these experiments were directly performed in conjunction with matched p300i-treated (24 hours) samples (shown with lower opacity). All RNA-Seq experiments were performed on 3 biological replicates that were raised from individual wells (altogether 24 RNA-Seq samples per model). (C-D) Variance by nonsupervized hierarchical clustering of the 100 most variable genes in DMSO, BETi_72h, IC50_r, and IC90_r isogenic SKNO1 (C) and OCI-AML3 (D) cells. (E-F) Assessment of cell proliferation of the indicated isogenic SKNO1 (E) and OCI-AML3 (F) cell lines after 72 hours (for SKNO1) and 120 hours (for OCI-AML3) of p300i treatment. Shown are mean percentages normalized to DMSO-treated controls and SD from 3 biological replicates.