Conclusion: Overall, we showed that the Bcl-2 signature could predict the prognosis of patients with DLBCL, and that ALPK1 could be a promising target for sensitizing patients with DLBCL to venetoclax therapy.<h4>Methods</h4>The 'WGCNA' package was used to comprehensively screen for Bcl-2 inhibitor-resistant genes (Bcl-2RGs) and the Bcl-2RGs signature was established using LASSO regression analysis with ten-fold cross-validation. This evidence concerns the gene ALPK1 and diffuse large B-cell lymphoma.