Fig. 5: Co-activation of CXCR4 and TCL1 governs a distinct oncogenic transcriptional program in B cells.
From: CXCR4 hyperactivation cooperates with TCL1 in CLL development and aggressiveness
a Outline of experimental setup for RNA sequencing of splenic and bone marrow pre-malignant B cells (WT, n = 5; CXCR4C1013G, n = 5; Eµ-TCL1, n = 5; Eµ-TCL1;CXCR4C1013G, n = 5). b Venn diagram showing overlap of significantly enriched pathways (padj < 0.05) for curated gene sets listed in MsigDB [63, 64] of indicated genotypes vs. WT B cells as determined by gene set enrichment analysis (GSEA). c GSEA of Eµ-TCL1;CXCR4C1013G vs. Eµ-TCL1 CD19+ B cells showing normalized enrichment scores (NES) and false discovery rates (FDR) for curated gene sets listed in MsigDB [63, 64]. d Selection of differentially expressed genes (DEG) with adjusted P value (padj) < 0.05 of Eµ-TCL1;CXCR4C1013G vs. Eµ-TCL1 CD19+ B cells. e GSEA showing enrichment of a Richter’s transformation signature [43] in Eµ-TCL1;CXCR4C1013G B cells. f Kaplan–Meier plots of overall survival (OS) and time to treatment (TTT) in a cohort of CLL patients, for patients with high vs. low enrichment of upregulated genes from CXCR4 signatures (CXCR4C1013G vs. WT and Eµ-TCL1;CXCR4C1013G vs. Eµ-TCL1) (TTT CXCR4C1013G vs. WT, n = 105 high, n = 103 low; OS CXCR4C1013G vs. WT and Eµ-TCL1;CXCR4C1013G vs. Eµ-TCL1, n = 105 in each group; TTT Eµ-TCL1;CXCR4C1013G vs. Eµ-TCL1, n = 104 in each group). P values of logrank (Mantel–Cox) test are shown.
