Novel therapeutic targets in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) represents the most frequent lymphoma subtype and is considered a heterogeneous diagnostic category [1]. Using gene expression profiling, two major molecular subtypes termed germinal centre B-cell-like (GCB) DLBCL and activated B-cell-like (ABC) DLBCL can be distinguished [2]. Their gene expression profiles suggest that they arise from B-cells at different stages of differentiation. The GCB DLBCLs appear to originate from germinal centre B-cells, whereas the ABC DLBCLs may arise from post-germinal-centre B-cells that are in transition to being differentiated into plasma cells. Intriguingly, these two subtypes differ not only with respect to the expression of thousands of genes, but also utilise different oncogenic pathways and have significantly different survival rates following therapy [3,4]. ABC DLBCLs are characterised by inferior survival compared with GCB DLBCL patients when treated with a combined approach of the anti-CD20 antibody rituximab and CHOP chemotherapy [5].