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. 2019 Nov 7;105(10):2420–2431. doi: 10.3324/haematol.2019.224956

Figure 3.

Figure 3.

Molecular perturbation triggered by ARQ531 in acute myeloid leukemia cells. (A) Heatmap for the highest 50 down- and up-regulated genes (P<0.0001) following ARQ531 treatment of OCI-AML3 cells. (B) Volcano plot of RNA-sequencing of drug- versus dimethylsulfoxide-treated cells in OCI-AML3 showing that 377 and 852 genes were significantly up- and down-regulated, respectively, with a fold change (FC) >2. (C) Table of the ten most significantly enriched gene sets, from the Hallmark collection, enriched with genes downregulated by ARQ531 in acute myeloid leukemia (AML) cells. Number of genes in each set (n), the normalized enrichment score (NES), and the test of statistical significance of the false discovery rate (FDR) q value are highlighted. (D) Enrichment plots of the top four most significantly enriched gene sets (MYC-related) in transcriptional profiles of AML cells treated (right) or untreated (left) with ARQ531. (E) Connectivity score generated by the LINCS L1000 Characteristic Direction Signature Search Engine tool, which compared the ARQ531-derived transcriptional profile against 10,000 “perturbagen” signatures (corresponding to shorthairpin RNA, open reading frame and compounds). Top-ranked scores of relevant results are indicated by arrows. HDACi: histone deacetylase inhibitor.