Gene set enrichment analysis (GSEA) of our multi-omics data revealed SpiD3 influenced various pathways highly relevant to CLL survival, proliferation and TME interplay such as “BCR signaling,” “NFκB signaling,” “cytokine signaling,” “E2F and MYC targets,” “oxidative stress,” “DNA damage,” “P53 pathway” and modes of cell death like “apoptosis” (Fig. 2B; Supplementary Fig. S2B and S3C). Here, MYC is linked to B-cell chronic lymphocytic leukemia.