BCL11A expression worsens the prognosis of DLBCL and its co-expression with C-MYC predicts poor survival

Abstract

Non-Hodgkin's lymphoma (NHL) is a significant global malignancy, with diffuse large B cell lymphoma (DLBCL) being the most prevalent subtype, accounting for 25–50 % of newly diagnosed cases in China. Despite a 60 % survival rate achieved with R-CHOP regiment for DLBCL, approximately 40 % of patients experience relapse or develop resistance to treatment. While the oncogenic transcription factor B-cell chronic lymphocytic leukaemia/lymphoma 11 A (BCL11A) has been implicated in various tumors, its specific role in DLBCL remains unclear. In this study, we conducted retrospective histomorphological and immunophenotypic analyses on paraffin sample tissues and collected fresh tissue samples for protein and mRNA analyses to investigate the relationship between BCL11A and DLBCL. Additionally, we classified DLBCL into subtypes based on cells of origin (COO) and examined the expressions of BCL11A, C-MYC, P53 and other protein expressions to better understand the factors contributing to poor clinical outcomes in DLBCL. Our findings revealed elevated BCL11A expression in DLBCL, with increased expression associated with worse prognosis and higher C-MYC expression. Patients exhibiting co-expression of C-MYC and BCL11A had significantly lower survival rates compared to those with singular expression. Furthermore, BCL11A protein expression levels demonstrated significant associations with P53 and C-MYC protein expression levels in the Germinal Center B-cell-like (GCB) subtype. These findings suggest that BCL11A may serve as a potential prognostic marker and therapeutic target for DLBCL.