Figure 5.

Transcriptional profiling reveals close correlation to human peripheral T-cell lymphoma. (A) CD8⁺ T-cell RNA-sequencing (performed with Illumina HiSeq2500) analysis showing the number of significantly (left) up- and (right) down-regulated genes in wildtype (wt), cS5A^lo and cS5A^hi CD8⁺ T cells obtained from lymph nodes (n=5/genotype; adjusted P-values <0.1, log₂ fold change >1 and <-1). (B) Summary of gene set enrichment analysis (GSEA) of hallmark gene sets enriched in cS5Ahi vs. cS5A^lo CD8⁺ T cells [false discovery rate (FDR) ≤0.25, adjusted P-value ≤0.05)]. (C) RNA isolated from CD8⁺ T cells of wt (n=10), hSTAT5B (n=4), hSTAT5B^N642H, cS5A^lo and cS5A^hi (all n=5) mice were subjected to RNA-sequencing. Heatmap of genes deregulated in a comparison of all genotypes to wt controls (n=1,055) clustered for up- and down-regulated genes specific to individual conditions, as well as for genes shared between hSTAT5B^N642H and cS5A^hi. Scaled, rlog transformed normalized counts from DESeq2 were used for the analysis. (D) Venn diagram of differentially expressed genes in cS5A^hi vs. wt and hSTAT5B^N642H vs. wt CD8⁺ T cells (adjusted P-values <0.1, log₂ fold change >1 and <-1). (E) GSEA of STAT5B^N642H and cS5A^hi expression data shows a correlation to peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) with cytotoxic T-cell features. NES: normalized enrichment score. The gene set was compiled from literature.^6,7