Bulk RNA-seq reveals the landscape of drug effects in ex vivo–treated T-PLL. (A) Schematic overview of the bulk RNA-seq experiment. T-PLL (n = 9) and T-LGL (n = 1) samples were treated either with birinapant (200 nM), nutlin-3a (2500 nM), motolimod (200 nM), selinexor (200 nM), everolimus (200 nM), ruxolitinib (200 nM), ibrutinib (100 nM), bafilomycin A1 (50 nM), pomalidomide (50 nM), dacinostat (5 nM), venetoclax (5 nM), or DMSO for 24 hours followed by RNA extraction, library preparation, and sequencing. (B) Directed network of significantly DEGs (FDR < 10%, |log2FC| > 0.25) showing the upregulated and downregulated genes in T-PLL (n = 9) and T-LGL (n = 1) samples after drug treatment relative to DMSO. In this network, each grey node (dot) corresponds to a DEG, with edges (lines) indicating the treatment(s) (colored nodes) that significantly affected the expression (upregulation = red, downregulation = blue). DEGs that are affected by the same treatments (upregulated or downregulated) are grouped together. Edge thickness indicates the adjusted P value. (C) Bar plot showing the number of significantly DEGs (FDR < 10%, |log2FC| > 0.25) after drug treatment relative to DMSO. Upregulated genes are shown as red, downregulated genes as blue. (D) Corresponding bar plot showing the number of upregulated and downregulated gene sets. (E) Dot plot showing the top 5 upregulated and downregulated gene sets per treatment (FDR < 10%, ≥10 overlapping genes). Dot size indicates the number of overlapping genes between the DEGs and the gene set. Coloring indicates the −log10 adjusted P value with direction (upregulation = red, downregulation = blue). Dots are arranged by hierarchical clustering. Gene sets belonging to key pathways are highlighted. (F-G) Volcano plots showing the upregulated and downregulated genes after nutlin-3a (F) and selinexor (G) treatment relative to DMSO. DEGs that are known to be upregulated upon p53 pathway activation and the TP53 gene are labeled.23 (H) Volcano plot showing the upregulated and downregulated genes after birinapant treatment relative to DMSO. DEGs that are part of the TNF-α and NF-κB pathways are labeled.24-27 (I) Dot plot showing expression changes of DEGs that belong to the TNF-α, TLR, and NF-κB pathways.24-27 Coloring indicates the −log10 adjusted P value with direction (upregulation = red, downregulation = blue). Dots are arranged by hierarchical clustering. p.adj., adjusted P value.

Bulk RNA-seq reveals the landscape of drug effects in ex vivo–treated T-PLL. (A) Schematic overview of the bulk RNA-seq experiment. T-PLL (n = 9) and T-LGL (n = 1) samples were treated either with birinapant (200 nM), nutlin-3a (2500 nM), motolimod (200 nM), selinexor (200 nM), everolimus (200 nM), ruxolitinib (200 nM), ibrutinib (100 nM), bafilomycin A1 (50 nM), pomalidomide (50 nM), dacinostat (5 nM), venetoclax (5 nM), or DMSO for 24 hours followed by RNA extraction, library preparation, and sequencing. (B) Directed network of significantly DEGs (FDR < 10%, |log2FC| > 0.25) showing the upregulated and downregulated genes in T-PLL (n = 9) and T-LGL (n = 1) samples after drug treatment relative to DMSO. In this network, each grey node (dot) corresponds to a DEG, with edges (lines) indicating the treatment(s) (colored nodes) that significantly affected the expression (upregulation = red, downregulation = blue). DEGs that are affected by the same treatments (upregulated or downregulated) are grouped together. Edge thickness indicates the adjusted P value. (C) Bar plot showing the number of significantly DEGs (FDR < 10%, |log2FC| > 0.25) after drug treatment relative to DMSO. Upregulated genes are shown as red, downregulated genes as blue. (D) Corresponding bar plot showing the number of upregulated and downregulated gene sets. (E) Dot plot showing the top 5 upregulated and downregulated gene sets per treatment (FDR < 10%, ≥10 overlapping genes). Dot size indicates the number of overlapping genes between the DEGs and the gene set. Coloring indicates the −log10 adjusted P value with direction (upregulation = red, downregulation = blue). Dots are arranged by hierarchical clustering. Gene sets belonging to key pathways are highlighted. (F-G) Volcano plots showing the upregulated and downregulated genes after nutlin-3a (F) and selinexor (G) treatment relative to DMSO. DEGs that are known to be upregulated upon p53 pathway activation and the TP53 gene are labeled.23 (H) Volcano plot showing the upregulated and downregulated genes after birinapant treatment relative to DMSO. DEGs that are part of the TNF-α and NF-κB pathways are labeled.24-27 (I) Dot plot showing expression changes of DEGs that belong to the TNF-α, TLR, and NF-κB pathways.24-27 Coloring indicates the −log10 adjusted P value with direction (upregulation = red, downregulation = blue). Dots are arranged by hierarchical clustering. p.adj., adjusted P value.

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