Bcl-6-dependent risk stratification by nuclear expression of Peli1 in diffuse large B-cell lymphoma.

Abstract

Background/Aim: Peli1 is an E3 ubiquitin ligase involving lymphomagenesis by lysine 63 ubiquitination-mediated stabilization of Bcl-6 with in diffuse large B-cell lymphoma (DLBCL). Materials and Methods: We categorized nuclear expression of Peli1 according to Bcl-6 status by immunohistochemistry in DLBCL (n=100), and analyzed clinicopathologic association with prognosis. Results: We established Bcl-6/Peli1 risk model composed of high risk (Bcl-6+/Peli1+ or Bcl-6-/Peli1-; n=64) and low risk (Bcl-6+/Peli1- or Bcl-6-/Peli1+; n=36). High risk group had more frequent non-GCB subtype (83% vs 64%; p=0.033) and Bcl-6-negativity (69% vs 28%; p<0.001) than low risk group. Univariate survival analysis for progression-free survival (PFS) and overall survival (OS) revealed Bcl-6/Peli1 risk group (p=0.026 and p=0.021) and other conventional variables including international prognostic index (IPI), stage, ECOG performance status, number of extranodal sites were significant prognostic factors, along with B symptoms for OS. In multivariate analysis for PFS, Bcl-6/Peli1 risk group (p=0.032; HR=3.29), IPI (p=0.013; HR=3.39) and ECOG PS (p=0.035; HR=3.08) were independent prognostic factors. In multivariate analysis for OS, Bcl-6/Peli1 risk group (p=0.048; HR=7.87) and IPI (p=0.001; HR=12.15) were associated with prognosis. Conclusions: DLBCL had distinctive risk groups according to pairs of nuclear Peli1 and Bcl-6 expression. These results suggest the potential role of Peli1 and Bcl-6 in risk assessment in DLBCL.