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

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.