Fig. 9: Pharmacologic and genetic HDAC3 inhibition results in reduced cell growth in high ERG-expressing human AML cells in vitro and in vivo. | Nature Communications

Fig. 9: Pharmacologic and genetic HDAC3 inhibition results in reduced cell growth in high ERG-expressing human AML cells in vitro and in vivo.

From: The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of the transcription factor ERG

Fig. 9: Pharmacologic and genetic HDAC3 inhibition results in reduced cell growth in high ERG-expressing human AML cells in vitro and in vivo.The alternative text for this image may have been generated using AI.

A HDAC3 inhibition using RGFP966 in low and high ERG-expressing AML cell lines. Mean number of cells relative to RGFP966 concentration 0 after 48 h in culture. n = 3 independent experiments in each experiment for each biological condition n = 1 biological independent sample, Data are represented as mean ± SEM, two-way ANOVA, Tukey’s multiple comparison test. The P-value comparing ERG-dependent vs. ERG-independent with HDAC3 inhibitor is P < 0.0001. B HDAC3 inhibition using RGFP966 in HNT-34 cells. Cells were counted by flow cytometry with a fixed volume of 60 µL in each condition out of 1 mL sample. n = 3 independent experiments in each experiment for each biological condition n = 1 biological independent sample, two-way ANOVA, Tukey’s multiple comparison test. The P-value comparing HNT34 against THP1 and MOLM-13 at 0.1 µM and 1 µM of RGP966 is P < 0.0001. C The effect of HDAC3 inhibition on SKNO1 cells in vivo. In one biological experiment, n = 12 animals in the treatment group (vehicle control or RGFP966), mean ± SEM, t-test, unpaired, Mann–Whitney. The bone marrow percentage of human CD45 cells was used to assess disease burden. The P-value comparing Vehicle control vs. RGFP966 group is P < 0.0001. D The effect of HDAC3 inhibition on ELF-153 cells in vivo. In one biological experiment, n = 7 animals in the vehicle group while n = 8 animals in the RGFP966 group, mean ± SEM, t-test, unpaired, Mann–Whitney. The bone marrow percentage of human CD45 cells was used to assess disease burden. The P-value comparing Vehicle control vs. RGFP966 group is P < 0.0011. E Inhibition of HDAC3 using CRISPR-dCas9 system in SKNO1 cells. The bone marrow percentage of human CD45 cells was used to assess disease burden. In one biological experiment, n = 12 animals in the treatment group (sgNT or sgHDAC3), mean ± SEM, t-test, unpaired, Mann–Whitney. The P-value comparing sgNT vs. the sgHDAC3 group is P < 0.0001. F Survival curve of NSG mice transplanted with SKNO1 cells after CRISPR-dCas9 targeting of HDAC3 (left panel, log-rank test, P-value = 0.0105). The percentage of bone marrow hCD45 cells as a measure of disease burden (right panel, mean ± SEM, t-test, unpaired, Mann–Whitney). In one biological experiment, n = 12 animals in the treatment group (sgNT or sgHDAC3). The P-value comparing sgNT-SKNO1 dCas9 vs. sgHDAC3-SKNO1 dCas9 group is P = 0.0098. G Survival curve of NSG mice transplanted with THP1 cells after CRISPR-dCas9 targeting of HDAC3 (left panel, n = 10 animals in each group). The percentage of bone marrow hCD45 cells as a measure of disease burden (right panel, flow cytometry analysis for n = 9 animals in each group, Wilcoxon test). In one biological experiment, n = 10 animals in the treatment group (sgNT or sgHDAC3). sgNT indicates non-targeting guide, * denotes P ≤ 0.05, ** denotes P ≤ 0.01, *** denotes P ≤ 0.001, **** denotes P ≤ 0.0001.

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