S.J. Horning Biomarkers in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous disease, affecting patients of all ages and presenting as limited or advanced disease in essentially any nodal or extranodal site in the body. Gene-expression profiling defined 3 molecular subtypes of DLBCL, termed germinal center B-cell-like (GCB), activated B-cell-like (ABC), and primary mediastinal B-cell lymphoma (PMBL). GCB-like DLBCL has a more favorable prognosis than ABC-like regardless of therapy with CHOP or RCHOP. 1,2 Additional genome-wide copy number analysis coupled with gene-expression profiling provide evident that the DLBCL subtypes are distinct diseases using different oncogenic pathways with implications for future treatments.3 Calculation of a survival score from a six-gene model is also predictive in the R-CHOP era, and this model has been successfully applied to routine formalin- fixed paraffin embedded tissue.4 To date, it has not been possible to reliably replicate the cell of origin with routine immunohistochemistry, in part due to lack of reproducibility with markers such as bcl-6.5,6 Recent data suggest that a 9 microRNA signature can differentiate the two subtypes of DLBCL and that some of the microRNAs in this signature correlate with clinical outcome.7