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Neoplastic transformation of germinal center B (GCB) cells may give rise to a variety of different B cell lymphoma subtypes, most of which show substantial heterogeneity in terms of genetic alterations and clinical features. The mutations observed in cancer-related genes in GCB cells are related to abnormalities in the immunogenetic mechanisms associated with germinal center reaction. Recent studies have rapidly identified genomic alterations in B cell lymphomas that may be useful for better subclassification, noninvasive diagnosis, and prediction of response to therapy. The WHO recognizes different lymphoma subsets classified within 2 major categories of B cell lymphoma: Hodgkin's lymphoma (HL) and B cell non-Hodgkin's lymphoma (NHL), each with distinct genetic aberrations, including chromosomal translocations, copy number abnormalities, or point mutations. Next-generation sequencing-based technologies have allowed cancer researchers to identify somatic mutations and gene expression signatures at a rapid pace so that novel diagnostic or prognostic biomarkers, as well as therapeutic targets, can be discovered much faster than before. Indeed, deep sequencing studies have recently revealed that lymphoma-specific somatic mutations may be detected in cell-free circulating DNA obtained from the peripheral blood of B cell lymphoma patients, suggesting the possibility of minimally invasive diagnosis, monitoring, and predicting response to therapy of B cell lymphoma patients. In this study, the current status of the recurrent genetic aberrations observed during diagnosis and/ or relapse in HL and the major subtypes of B cell NHL (i.e. diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, and Burkitt lymphoma) are discussed to shed light on their potential use as noninvasive diagnostic or prognostic biomarkers and to reveal their role in lymphomagenesis as a target in therapy for newly diagnosed and chemotherapy-resistant cases.

CD19-targeted chimeric antigen receptor-T (CAR-T) cells with CD28 or 4-1BB (28z CAR-T and BBz CAR-T) have shown great promise to treat relapsed or refractory (r/r) B cell non-Hodgkin’s lymphoma (B-NHL). However, comparison of their clinical outcomes has never been reported. This study investigated their efficacy and adverse events in B-NHL therapy. Six patients with r/r B-NHL were initially enrolled and infused with 28z or BBz CAR-T cells at a dose of 0.75–5 × 105/kg. These CAR-T cells showed similar antitumor efficacies, with a complete response (CR) rate of 67% within 3 months. BBz CAR-T was well tolerated. However, severe cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in the 28z CAR-T cohort, resulting in the termination of further evaluation of 28z CAR-T. Three more patients were enrolled to investigate BBz CAR-T cells in-depth at an escalated dose (1 × 106/kg). All cases achieved CR within 3 months, and only grade 1/2 adverse events occurred. This study suggests that 4-1BB is more beneficial for the clinical performance of CAR-T cells than CD28 in CD19-targeted B-NHL therapy, at least under our manufacturing process., Graphical Abstract