Biological heterogeneity in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is heterogeneous both in clinical outcomes and the underlying disease biology. Over the last 2 decades, several different approaches for dissecting biological heterogeneity have emerged. Gene expression profiling (GEP) stratifies DLBCL into 3 broad groups (ABC, GCB, and DZsig/MHG), each with parallels to different normal mature B cell developmental states and prognostic implications. More recently, several different genomic approaches have been developed to categorize DLBCL based on the co-occurrence of tumor somatic mutations, identifying more granular biologically unified subgroups that complement GEP-based approaches. We review the molecular approaches and clinical evidence supporting the stratification of DLBCL patients based on tumor biology. By offering a platform for subtype-guided therapy, these divisions remain a promising avenue for improving patient outcomes, especially in subgroups with inferior outcomes with current standard-of-care therapy.