TNFRSF14 mutation

The optimal treatment for DH/TH lymphoma remains unclear, although outcomes are inadequate with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) alone...The initial dose of each drug in this regimen is as follows (repeat every 21 days, 6 cycles in total): rituximab: 375mg/m 2, d0; vindesine 4mg, d1; epirubicin 75mg/m 2, d1 (or liposomal doxubicin 35mg/m 2, d1); cyclophosphamide: 750mg/m 2, d1; prednisone: 100mg, d1-5; selinexor 60mg orally once a week...Dynamic testing of ctDNA demonstrated deep remission to chemotherapy. Based on the encouraging results of the current study, a large scale, multicenter trial is needed to further investigate this promising regimen.

2022 Feb 1; 40(4):369-381). Performance of CLMA on a larger number of tumor samples from DLBCL/HGBL pts subsequently treated with CART19, which is planned, may be informative.

Pediatric-type follicular lymphoma (PTFL) is characterized by MAP2K1, TNFRSF14 and/or IRF8 mutations, whereas large B-cell lymphoma with IRF4 rearrangement is now recognized as a distinct entity different from PTFL. Ultimately, the better understanding of FL biology and heterogeneity should help to understand the clinical differences and help guiding patient management and treatment decisions.

Since the introduction of rituximab (R), an anti-CD20 antibody more than 20 years ago, and other new drugs, the current median overall survival (OS) often extends beyond two decades...The GALEN trial showed that obinutuzumab (O) is a good alternative to R, in combination with lenalidomide. Most patients with symptomatic high tumor burden, according to the GELF-criteria, are still treated with R or O in combination with chemotherapy (CVP, CHOP, or bendamustine)...However, tazemetostat has modest activity as a single agent but is well tolerated and combination therapies are under evaluation...Trials are ongoing also in the upfront setting (epcoritamab + R2 and mosunetuzumab + lenalidomide). Cell-therapies will be discussed further in the next talk

GNA13 mutant was significantly associated with an increased risk of death (HR: 6.6 [95%CI: 2.1-20.6]; p=0.0011) and shorter overall survival (p=0.0340). At the time of relapse or refractory disease, three genetic subgroups of DLBCL patients were delineated, which could help advance precision molecular medicine programs.

In-situ follicular B-cell neoplasm, pediatric-type FL, duodenal-type FL and primary cutaneous follicle center lymphoma are categorized as discrete entities. In addition, novel findings concerning underlying biological mechanisms in the pathogenesis of early and systemic follicular lymphoma will be presented.

Here, we identified novel genetic subtypes that are distinguishable not just by unique sets of mutations, but also by their clinical associations and methylation profiles. The novel genetic profiles shed light on core pathways distinctly tied to each subtype. Targeted DNA sequencing of a limited gene panel represents a potentially accessible method of subtyping FL in the clinical setting, with implications for the understanding of responses to targeted therapy.

We present here a refined classification of DLBCL genetic subgroups that combines previously described classification algorithms and extends it to allow classification of more tumors into additional subgroups that preserve the major divisions of existing systems. This represents an important advancement that will facilitate further understanding of genomic complexity in this disease.

A pool of REL overexpressing GC B-cell was generated after tamoxifen administration and T-cell-dependent antigen stimulation with sheep red blood cells (SRBC)...Conclusion We bring strong experimental arguments showing that increased c-Rel expression in GC B-cell favors their survival for several months, and would thus be a primary event. We suspect that additional oncogenic events are probably needed for tumor clonal expansion such as BCL2 , EZH2 , CREBBP , TNFRSF14 and/or c-Myc dysregulation.

Overall, our findings provide insights for the application of targeting OX40, or a combined OX40 agonists and first-line immunochemotherapy in DLBCL patients.

Both CD274 and TNFRSF14 genetic changes were significantly associated with Hashimoto's thyroiditis (p = 0.01, p = 0.04, respectively), and CD274 mutation/deletion additionally associated with increased erythrocyte sedimentation rate (p = 0.0001). In conclusion, CD274/TNFRSF14 inactivation in thyroid MALT lymphoma B-cells may deregulate their interaction with T-cells, promoting co-stimulations and impairing peripheral tolerance.

These results show that, clinically and biologically, c-Rel is the pivotal NF-κB subunit in the GCB-DLBCL subgroup. Functionally, c-Rel overexpression could directly promote DLBCL tumorigenesis without need for further activation signals.