Figure 3.

The near future for B-cell lymphoma patients: genetic signatures lead to personalized treatments. Recent studies have identified genetic signatures in diffuse large B-cell lymphoma (DLBCL) patients that can be used to predict outcome and therapy response. In the near future, a combination of newly adapted routines in daily clinical practice (left) and basic research (right) are very likely to lead to personalized treatments for B-cell lymphoma patients, based on the genetic profile of their biopsies. To this end, gene edition of DLBCL cell lines in the laboratory will enable the replication of the DLBCL genetic subtypes (GS) identified in patients (BN2, N1, EZB, MCD, and ST2). 3D organoid-based drug screenings will establish the sensitivities of the different genetic variants to single drugs or drug combinations, at the dose and posology levels, while maintaining the lymphoma microenvironment and intercellular interactions. Once a GS has been matched to a certain treatment regimen, drug sensitivity should be validated in organoids derived from fresh patient biopsies (patient derived organoids, PDOs). Inclusion of biopsy sequencing using targeted panels of selected genes as part of the daily clinical routine will eventually allow personalized treatments to be directly assigned based on the GS of patient biopsies, optimized treatment-response rates, and improved overall survival. FFPE: formalin-fixed, paraffin-embedded.