PI3K/AKT addiction in subsets of diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoma subtype and accounts for approximately 30–40% of all cases in adults.1 DLBCL represents a heterogeneous diagnostic category with respect to morphology, biology, and clinical outcome.1 The use of gene expression profiling significantly improved our understanding of this heterogeneity, as 2 major molecular DLBCL subtypes that arise from different stages of B-cell differentiation were identified by this approach.2 Germinal center B-cell-like (GCB) DLBCLs are derived from germinal center B-cells and, accordingly, express genes such as BCL6 or LMO2 that are detectable in normal germinal center B-cells. In contrast, activated B-cell-like (ABC) DLBCLs originate from activated B-cells that are in the process of differentiation into plasma cells. Intriguingly, these entities not only differ with respect to their gene expression profile, but they are also characterized by significant differences in survival when treated with standard therapy.3 Finally, ABC and GCB DLBCLs are addicted to different oncogenic pathways due to divergent genetic aberrations.

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