Transcriptomic characterization of CXCR4C1013G and Eµ-TCL1;CXCR4C1013G CD19+ B cells

Aberrant CXCR4 activity has been implicated in lymphoma pathogenesis, disease progression and resistance to therapies. Using a mouse model with a gain-of-function CXCR4 mutation (CXCR4C1013G) that hyperactivates CXCR4 signaling, we identified CXCR4 as a crucial activator of multiple key oncogenic pathways. CXCR4 hyperactivation furthermore resulted in an expansion of transitional B1 lymphocytes, which represent the precursors of chronic lymphocytic leukemia (CLL). Indeed, CXCR4 hyperactivation led to a significant acceleration of disease onset and a more aggressive phenotype in the murine Eµ-TCL1 CLL model. Hyperactivated CXCR4 signaling cooperated with TCL1 to cause a distinct oncogenic transcriptional program in B cells, characterized by PLK1/FOXM1-associated pathways. In accordance, Eµ-TCL1;CXCR4C1013G B cells enriched a transcriptional signature from patients with Richter’s syndrome, an aggressive transformation of CLL. In summary, we here identify CXCR4 hyperactivation as a co-driver of an aggressive lymphoma phenotype. Here we make available the transcriptomic data of CD19+ B cells from bone marrow and spleen of 6-week-old WT, CXCR4C1013G, Eµ-TCL1 and Eµ-TCL1;CXCR4C1013G mice. 4 genotypes: WT, CXCR4C1013G, Eµ-TCL1, Eµ-TCL1;CXCR4C1013G; 2 tissues: CD19+ B cells from spleen, CD19+ B cells from bone marrow; 5 replicates per biological group; 40 samples in total