# Overexpression of CDCA2 in Diffuse Large B-Cell Lymphoma Promotes Cell Proliferation and Bortezomib Sensitivity

## TL;DR

This study shows that high CDCA2 expression in DLBCL patients improves survival with bortezomib treatment and that CDCA2 influences bortezomib sensitivity in lymphoma cells.

## Contribution

The study identifies CDCA2 as a novel marker linked to bortezomib response in DLBCL and demonstrates its functional role in drug sensitivity.

## Key findings

- High CDCA2 expression in DLBCL patients correlates with better survival when treated with RB-CHOP.
- CDCA2 knockout reduces DLBCL cell proliferation and bortezomib sensitivity in vitro and in vivo.
- CDCA2 is overexpressed in DLBCL compared to non-malignant tissue and in specific subtypes like GCB and double-expressor patients.

## Abstract

Numerous clinical trials have attempted to improve first-line R-CHOP treatment of diffuse large B-cell lymphoma (DLBCL) through the addition or substitution of drugs. The REMoDL-B trial, testing the addition of bortezomib (RB-CHOP), revealed that ABC and molecular high-grade DLBCL patients benefit from bortezomib. The aim of this study was to achieve a better understanding of the bortezomib response in DLBCL through a functional investigation of clinically identified markers. A retrospective analysis of transcriptional and clinical data from the REMoDL-B trial was conducted to identify genes associated with bortezomib response, identifying CDCA2. DLBCL patients with high expression of CDCA2 had a superior survival outcome when treated with RB-CHOP in comparison to R-CHOP, whereas no difference in outcome was observed for patients with low CDCA2. Moreover, CDCA2 was found to be overexpressed in DLBCL compared to non-malignant tissue, and to have higher levels in GCB and MYC/BCL2 double-expressor patients. Functional in vitro and in vivo studies revealed that knockout of CDCA2 decreased DLBCL cell proliferation and a bortezomib dose–response analysis showed less sensitivity in CDCA2 knockout cells compared to control cells. This study shows that DLBCL patients with high CDCA2 expression benefitted from the addition of bortezomib to R-CHOP and functional studies documented a direct impact of CDCA2 on the bortezomib response in DLBCL cells.