Molecular signatures in the diagnosis and management of diffuse large B-cell lymphoma

Purpose of Review: This review summarizes recent data on the relevance of molecular subtypes of diffuse large B-cell lymphoma to clinical management and the potential to use subtyping to direct therapy. Recent Findings: Gene expression profiling and immunohistochemistry can distinguish between diffuse large B-cell lymphomas arising from germinal center-derived B-cells (GCB type) or activated B-cells (ABC type) with a high degree of concordance. This biologic distinction is highly relevant clinically. The ABC type is associated with a poor prognosis and is characterized biologically by constitutive activation of the NF-κB pathway and chronic activation of the B-cell receptor pathway, both of which confer an antiapoptotic phenotype and chemoresistance. Emerging preclinical and clinical data suggest that these pathways can be targeted specifically in ABC-type disease. New molecular techniques may allow further refinement of this approach. Summary: Recent data support the concept that molecular subtyping of diffuse large B-cell lymphoma is clinically relevant and likely to be incorporated into diagnostic and therapeutic algorithms. The availability of widely applicable and reproducible techniques for determining molecular subtype will be essential.