Anti-tumor activity of the combination of bendamustine with vorinostat in diffuse large B-cell lymphoma cells

Abstract

Current standard-of-care therapy for diffuse large B-cell lymphoma (DLBCL) results in up to 40% of patients who either relapse or develop refractory disease. In this setting, further therapeutic improvements are needed. This study analyzed the in vitro effects of the combination of bendamustine with the histone deacetylase inhibitor vorinostat in DLBCL cells. This combination enhanced histone acetylation and double strand DNA breaks resulting in an additive to synergistic cytotoxic effect in both ABC- and GCB-type DLBCL cells, independently of their TP53 mutational status. These results support the rationale for considering bendamustine and vorinostat combination as a novel approach in DLBCL treatment.

Keywords::

• Bendamustine
• vorinostat
• diffuse large B-cell lymphoma
• TP53
• histone deacetylase inhibitor

Acknowledgments

This work was supported by grants from AECC Cataluña 2009, 2014 SGR 567, Instituto de Salud Carlos III FEDER (PT13/0010/0005) and the “Xarxa de Bancs de tumors” sponsored by Pla Director d’Oncologia de Catalunya (XBTC). Concepción Fernández-Rodríguez received a fellowship from the Ministry of Economy and Competitiveness of Spain (PFIS grant FI11/00353).

Potential conflict of interest

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