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>Results</h4>The Bcl-2 signature is an effective prognostic prediction model using Gene Expression Omnibus data analysis. The gene discussed is ALPK1; the disease is diffuse large B-cell lymphoma.