DLBCL Cell of Origin: What Role Should It Play in Care Today?

Diffuse large B-cell lymphoma (DLBCL) is curable in about two-thirds of patients. Research has focused on determining which patients have less favorable prognoses so that they can be considered for novel targeted-treatment strategies. In 2000, gene expression profiling was used to define two principal DLBCL molecular subtypes, germinal center B-cell-like (GCB) and activated B-cell-like (ABC). Patients with GCB DLBCL have more favorable outcomes than those with ABC DLBCL when treated with standard immunochemotherapy. Alternate strategies to characterize molecular subtype include approximation with immunohistochemistry algorithms, and more recently the NanoString gene expression platform. Numerous studies have investigated novel agents in DLBCL with respect to GCB and ABC (or non-GCB) subtypes, but R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the standard of care for most patients. Here we review the methods of determining cell of origin (COO); use of COO in clinical practice; clinical trials in DLBCL according to COO; and future directions of tailoring treatment, including alternate categorization of genetic subtypes or clusters in DLBCL.