Fig. 7

ARV-825 reduces c-Myc expression in T-ALL cells. a Volcano plot of RNAseq analysis of gene expression changes in 6 T-CEM and Jurkat cells after ARV-825 treatment. Genes highlighted in red form the up-fold changes, blue indicates down regulated genes and black on behalf of unchanging genes. b Heat-map view of the top differentially expressed genes with 20 upregulated and 20 downregulated in 6 T-CEM and Jurkat cells treatment with 1 μM ARV-825 for 48 h (log2FC > 1, P < 0.05). Downregulated genes belong to multiple pro-survival pathways including c-Myc targets. Each column represents a different sample and each row represents a single gene. Color changes within a row indicate expression levels relative to the average of the same population. Red indicates upregulation and blue indicates downregulation. c ChIP-seq analysis showed H3K27Ac signal density down regulated with ARV-825 treatment in 6 T-CEM cells. Downregulated genes, IGLL1 and CARMIL2, were confirmed by ChIP-seq analysis in the same T-ALL cells. Results showed that H3K27Ac modification was inhibited significantly with ARV-825 treatment. d GSEA plots showing the enrichment of genes in HALLMARK_MYC_TARGETS gene set in RNA-Seq following ARV-825 treatment in 6 T-CEM and Jurkat cells. e Western blot analysis of c-Myc expression in 4 T-ALL cells. f Western blot analysis showed c-Myc protein was down regulated by treatment with ARV-825 at different concentration in 4 T-ALL cells. g Western blot analysis showed c-Myc protein was downregulated by treatment with 1 μM ARV-825 at different times in 4 T-ALL cells