In summary, unbiased RNA-sequencing-based transcriptome analyses reveal possible clues to the mechanistic basis of the ibrutinib/venetoclax synergy, and specifically point to the anti-apoptotic Bcl-2 family members Bcl-XL and Bcl-2A1 as drivers of alternative survival pathways that must be overcome for efficient killing of Bcl-2-expressing DLBCL cells by venetoclax. This evidence concerns the gene BCL2L1 and diffuse large B-cell lymphoma.