Identifying Biomarkers for Diffuse Large B-Cell Lymphoma Subtypes

Abstract

Diffuse Large B-cell Lymphoma (DLBCL) is the most common lymphoid malignancy in adults, accounting for ~35% of Non-Hodgkin’s lymphoma cases worldwide. Several classification systems have been proposed based on shared morphology, immunophenotype, genetic alterations, clinical outcomes, etc., to decipher the mechanisms of pathogenesis and design suitable therapy. Classification of DLBCL into cell-of-origin (COO) subtypes, Germinal Centre B-cell (GCB) and Activated B-cell (ABC), has been traditionally defined as lowand highrisk patient groups respectively when treated with chemotherapy [1]. Several previous studies have shown a diverse set of genetic and epigenetic factors affecting few key pathways in each subtype. For example, the GCB subtype is mostly characterized with alterations in chromatinmodifying enzymes, activated PI3K pathway, disruption of Gα migration pathway components and frequent structural variants of BCL2 gene, while ABC subtype is often associated with increased NF-κB activity, altered BCR signalling, perturbed terminal B cell differentiation, etc. The differences in the genetic profiles of the two subtypes have been associated with differential response to treatment, with ABC subtype exhibiting poorer outcomes compared to GCB subtype when treated with standard rituximab, cyclophosphamide, doxorubicin (Adriamycin), vincristine (Oncovin) and prednisone (R-CHOP) immuno-chemotherapy. Moreover, relapsed/refractory DLBCL is observed in ~30-40% of the treated cases.