III. Applying molecular phenotyping in practice

Morphologic heterogeneity in diffuse large B-cell lymphoma (DLBL) was recognized under historic classification systems for lymphoma, and the application of cytogenetics with in situ hybridisation gave some indication of the variable molecular pathogenesis, but it was really only with gene expression profiling that a biologically plausible way was found to characterize the different entities. The examination of a very large number of different mRNA sequences led to the first demonstration of groups with different prognosis according to their apparent cell of origin [1]. Since then, there has been a progressive accumulation of information about the molecular characteristics in the two main groups, germinal centre B-cell (GCB) type and activated B-cell (ABC) type, with genomic analyses [2–4] and RNA knockdown library screens [5–7] adding to knowledge of the different pathogenic pathways, and the potential targets for intervention using selective inhibitors. Retrospective studies have confirmed the worse prognosis for patients with ABC type DLBL [8,9], although when multivariate analyses are used, it is clear that some of the difference may well be related to older age at diagnosis and other adverse features of their presentation [10]. The challenge now is to use this information to improve the results of treatment for patients. This requires two key elements: a reliable test and an effective intervention. To what extent are these currently available, or about to become so?