New Targets for the treatment of mature B cell non Hodgkin lymphomas
Résumé
Whole exome sequencing (WES) by next generation sequencing (NGS) has completely redefined the genetic landscape of mature B‐cell non‐Hodgkin lymphomas (NHL) by identifying recurrent single nucleotide variants and providing new therapeutic opportunities. Some of these somatic mutation target genes that play a crucial role in B‐cell function (BCR signalling, NFκ‐B pathway, Toll‐like receptor signalling, and the PI3K pathway), immunity, cell cycle/apoptosis, or chromatin modification. Some driver mutations represent the Achilles Heel of the tumours and may be translated into therapeutic interventions. BCR signalling is targeted by inhibitors of the early components of the pathway, such as BTK, SYK, PKCβ, or PIK3δ, whereas the NF‐KB pathway is targeted by upstream and downstream inhibitors (proteasome/ubiquitin complex) or more pleiotropic agents (lenalidomide). In this review, following an overview of the somatic mutations reported in mature B‐cell malignancies, especially in diffuse large B‐cell lymphomas and Burkitt lymphomas in both adults and children, we focus on activating and clustered driver mutations targeting genes including MYD88, CD79A/B, EZH2, and CARD11 and discuss their clinical and therapeutic relevance in the precision medicine era.