Molecular Classification of Diffuse Large B-Cell Lymphoma: A Review of Pathogenetic Subtypes and Their Therapeutic Implications

Abstract

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma that accounts for many B-cell lymphomas. The molecular heterogeneity of DLBCL has been increasingly recognized on the different biological origins and varying clinical manifestations and treatment responses of this disease which makes the DLBCL an extremely heterogeneous group of lymphomas. Recent technological advances have been able to uncover the existence of different gene expression subtypes like germinal center B-cell-like and activated B-cell-like types and also genetic rearrangements involving MYC BCL2 BCL6, and multiple signaling pathways. This article updates the knowledge on molecular features and their relation to the different aspects of disease development, prediction of survival, identification of the disease, and choice of therapy. The current literature clearly illustrates the growing importance of specific medications, immunotherapies, and cell-based treatments for patients with relapsed or refractory disease. CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy is among the latest developments in treatment, and next-generation CAR-T cell platforms as well as their combinations with targeted therapy agents are very active areas for research. So, molecular profiling can bring risk stratification and individualized medicine. Finally, combining molecular findings with the clinical and the pathological pictures will probably be an important tool in managing patients with DLBCL. Also, this integrated approach is expected to help tailor the treatment more effectively in the future.