Driving toward precision medicine for B cell lymphomas: Targeting the molecular pathogenesis at the gene level. (June 2020)

• Record Type: Journal Article
• Authors: Chung, Clement
• Is Part Of: Journal of oncology pharmacy practice. Volume 26:Number 4(2020)
• Page Start: 943
• Page End: 966
• Publication Date: 2020-06
• Subjects: MYC -- BCL-2 -- BCL-6 -- MYD88 -- CARD11 -- epigenetics; Cancer -- Chemotherapy -- Periodicals; Clinical pharmacology -- Periodicals; 616.994061
• DOI: 10.1177/1078155219895079
• Languages: English
• ISSNs: 1078-1552

Abstract

Lymphomas are a diverse group of hematologic malignancies that arise from either T cell, B cell or the natural killer cell lineage. B cell lymphomas arise from gene mutations with critical functions during normal B cell development. Recent advances in the understanding of molecular pathogenesis demonstrate that many different recurrent genomic and molecular abnormalities and dysregulated oncogenic regulatory pathways exist for many subtypes of B cell lymphomas, both across and within histological subtypes. Pathogenetic processes such as (1) chromosomal aberrations, for example, t(14;18) in follicular lymphoma, t(11;14) in mantle cell lymphoma, t(8;14) in Burkitt lymphoma; dysregulations in signaling pathways of (2) nuclear factor- κB (NF-κB); (3) B cell receptor (BCR); (4) Janus kinase/signal transducers and transcription activators (JAK-STAT); (5) impaired apoptosis/cell cycle regulation due to mutated, rearranged or amplified MYC, BCL-2, BCL-6 proto-oncogenes; (6) epigenetic aberrations may contribute to pathogenesis. More studies are under way to elucidate the molecular heterogeneity underlying many types of lymphomas that account for variable responses to treatment, generation of subclones and treatment resistance. Although significant research is still needed, targeted therapy promises to provide new options for the treatment of patients with lymphomas. This article provides a non-exhaustive overview on the current understanding on the genetics of pathogenesis of B cell lymphomas and their therapeutic implications.