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K.N. Smitheman et al.
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Figure 3. RNA sequencing reveals differentiation gene signature with combination (COMBO). (A) Venn diagram depicting the overlap of significantly differentially expressed genes in the specific treatments [GSK2879552 + all-trans retinoic acid (ATRA) combination relative to dimethyl sulfoxide (DMSO) (light blue), ATRA relative to DMSO (yellow), and GSK2879552 relative to DMSO (blue)] for MOLM-13 (top) and OCI-AML3 (bottom) cell lines at day 2 (left) and day 4 (right). (B) Corresponding gene expression heatmaps depicting the union of genes from day 2 and day 4 Venn diagrams (from A) for MOLM-13 (top) and OCI-AML3 (bottom) cell lines. Values are row-mean centered, log2 normalized, gene expression data shown high (yellow) to low (blue). (C) Venn diagrams depicting the overlap of significantly differentially expressed genes for the GSK2879552 + ATRA combination relative to DMSO in each of the four cell lines, OCIAML-3, MOLM-13, MV-4-11, and THP-1. Data for dif- ferent time points are shown, day 2 (top, left), day 4 (top, right), and union of day 2 and day 4 (bottom). Red value indicates overlap of significant genes in all four cell lines for both days. (D) Gene expression heatmaps of overlapping combination versus DMSO genes in intersect (from C) for day 2 (top) and day 4 (bottom). Values are row-mean centered, log2 normalized, gene expression data shown high (yellow) to low (blue). (E) Barplots showing the top 10 KEGG pathways found to be signif- icantly enriched from genes in (C) in intersect (day 2, day 4 and union of day 2 and day 4 tested separately). Bars show the –log((False Discovery Rate P-value) on the x-axis and the MSigDB KEGG pathways identified as enriched in at least one timepoint on the y-axis. Red bars indicate pathways that were also identified as enriched in all four cell lines across both time points using an alternative method (Online Supplementary Figure S3D).
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haematologica | 2019; 104(6)