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. Author manuscript; available in PMC: 2025 Dec 24.
Published in final edited form as: Blood. 2025 Feb 13;145(7):748–764. doi: 10.1182/blood.2022019306

Figure 6. p300 regulates multiple downstream mediators of BET-inhibitor resistance.

Figure 6

A. Average binding curve profiles for p300 in the indicated isogenic SKNO1 with different degrees of BETi-resistance, centered at/around regulatory regions of the rescued (left panel) and evolution (right panel) genes.

B.-D. Examples of binding kinetics of p300 at ETV6 (a rescued gene) (B), CCR7 (an evolution gene) (C) and NCAM1 (an evolution gene) (D) in BETi-sensitive and BETi-resistant settings.

E. Continued from Figure 5B - Experimental approach to the assessment of transcriptional changes during the longitudinal scale of establishment of resistance to BETi and sensitivity towards p300i.

F. Longitudinal analysis of expression of SKNO1 evolution genes that code for ligands and signaling receptors, during all stages of resistance to BETi, with or without addition of p300i for 24h. Individual genes within the group were chosen based on their structural assignment per gene ontology analysis. Shown are average FPKM values from 3 biological replicates and SD.

G. Assessment of cellular viability after NCAM1 knockdown in the indicated SKNO1 isogenic cells for 120h. Shown are percentages normalized to Luc controls and SD from 3 biological replicates.

H. Longitudinal analysis of expression of all OCI-AML3-related “inflammation” genes, during all stages of resistance to BETi, with or without addition of p300i for 24h. Shown are average FPKM values from 3 biological replicates and SD.

I. Assessment of cellular viability after S100A9 knockdown in the indicated isogenic cells for 120h. Shown are percentages normalized to Luc controls and SD from 3 biological replicates.

J. Analysis of cellular viability after treatment with either DMSO or Paquinimod in the indicated OCI-AML3 isogenic cells for 72h. Shown are percentages normalized to DMSO-treated controls and SD from 3 biological replicates.

K. Longitudinal analysis of expression of all OCI-AML3-related “interferon” genes, during all stages of resistance to BETi, with or without addition of p300i for 24h. Shown are average FPKM values from 3 biological replicates and SD.

L. Analysis of cellular viability after STAT1 knockdown and DMSO- or p300i-treatment for 120h in the indicated isogenic cell lines. Shown are percentages normalized to DMSO and SD from 3 biological replicates.