Using an isogenic DLBCL cell model with high and low venetoclax sensitivity, we found that Bcl-XL is upregulated in venetoclax-resistant cells, while the cells do not become more sensitive to BIRD-2, a peptide that disrupts IP3R/Bcl-2 complexes and disrupts Bcl-2’s function at the ER. Here, BCL2L1 is linked to diffuse large B-cell lymphoma.