Skip to main content
. 2023 Jan 20;83(7):983–996. doi: 10.1158/0008-5472.CAN-22-2129

Figure 6.

Figure 6. The relative sensitivity of primary human CD34+ HSPCs and AML specimens defines a therapeutic window for SWI/SNF inhibition. Number of colonies formed by primary human (A) CD34+ HSPCs and (B) AML samples treated with BRM014 or DMSO and IC50 measurements. CD34+ HSPC curves overlayed in B for comparison, N = 3 per sample. C, Representative images of May-Grunwald Giemsa stained primary KMT2Ar and non-KMT2Ar leukemia cells from donor treated with BRM014 or DMSO. D, Representative flow cytometry histograms and (E) quantification of CD44 and myeloid differentiation markers in primary leukemias treated with BRM014 compared with DMSO control. F, Ranking of differential TF motif accessibility in primary AML specimens treated with 1 μmol/L BRM014 versus DMSO control. G, Accessibility at BENC module following treatment with DMSO or 1 μmol/L BRM014. H, MYC expression after treatment with BRM014 or DMSO measured by RT-qPCR. I, Quantification of accessible PU.1 motifs at intergenic and promoter sites in primary AML specimens treated with 1 μmol/L BRM014 or DMSO, N = 5 independent specimens with replicates. Error bars: mean ± SEM; *, P < 0.05; **, P < 0.01; ***, P < 0.001.

The relative sensitivity of primary human CD34+ HSPCs and AML specimens defines a therapeutic window for SWI/SNF inhibition. A and B, Number of colonies formed by primary human CD34+ HSPCs (A) and AML samples (B) treated with BRM014 or DMSO and IC50 measurements. CD34+ HSPC curves overlayed in B for comparison. N = 3 per sample. C, Representative images of May-Grunwald Giemsa–stained primary KMT2Ar and non-KMT2Ar leukemia cells from donors treated with BRM014 or DMSO. D and E, Representative flow cytometry histograms (D) and quantification (E) of CD44 and myeloid differentiation markers in primary leukemias treated with BRM014 compared with DMSO control. F, Ranking of differential TF motif accessibility in primary AML specimens treated with 1 μmol/L BRM014 versus DMSO control. G, Accessibility at BENC module following treatment with DMSO or 1 μmol/L BRM014. H,MYC expression after treatment with BRM014 or DMSO measured by RT-qPCR. I, Quantification of accessible PU.1 motifs at intergenic and promoter sites in primary AML specimens treated with 1 μmol/L BRM014 or DMSO. N = 5 independent specimens with replicates. Error bars, mean ± SEM. ***, P < 0.001.