Novel insights into the pathogenesis of molecular subtypes of diffuse large B-cell lymphoma and their clinical implications

Abstract

Introduction: Diffuse large B-cell lymphoma (DLBCL) represents a heterogeneous diagnostic category consisting of different molecular subtypes relying in their biology on distinct signaling pathways.Areas covered: This article provides an overview of the molecular understanding in DLBCL and highlights potential clinical implications reviewing relevant publications and clinical trials from PubMed and clinicaltrials.gov until August 2019.Expert opinion: Based on gene expression profiling, DLBCL can be divided in two broad subtypes, the activated B-cell-like (ABC) and germinal centre derived (GCB) DLBCL. Recent comprehensive genomic analyses revealed reproducible molecular clusters within the ABC/GCB classification and suggest a more profound molecular characterization to stratify patients within clinical trials. During the last couple of years, a multitude of novel targeted therapies has been developed, but so far without improving our current therapeutic standard of immunochemotherapy. Next to the limitation of toxic side effects and a more precise selection of patients, one of the greatest challenges will be to provide molecular characterization in a more time efficient way to enable a specific and individual treatment strategy.

Keywords: ABC; C1-C5 clusters; DLBCL; GCB; NF-κB; targeted therapy.