CARD11 mutation

To compare the safety and efficacy of zanubrutinib plus rituximab and lenalidomide (ZR2) and R-CHOP-like for elderly patients with newly diagnosed DLBCL, we conducted this single-center prospective study. Patients with gastrointestinal DLBCL have to be monitored closely by abdominal enhanced CT every cycle. Overall, ZR2 chemo-free regimen might be more appropriate for elderly DLBCL patients.

The application of rituximab has significantly enhanced the overall survival rates in patients with diffuse large B-cell lymphoma (DLBCL)...In addition, we revealed mutations in HIST2H2AB, BCL2, NRXN3, FOXO1, HIST1H1C, LYN and TBL1XR1 genes were only detected in initial diagnostic biopsies, mutations in the EBF1 gene were solely detected in the rrDLBCL patients. Collectively, this study elucidates some of the genetic mechanisms contributing to the progression of rrDLBCL and suggests that the presence of CD58 mutations might serve as a powerful predictive marker for relapse/refractory outcomes in primary DLBCL patients.

Immunophenotypically, the cases were predominantly GCB, in contrast to older adults (61%). In summary, we showed that molecular findings identified in the PCNSLs of the older patients were only sparingly present in pediatric and young adult patients.

Clinically significant findings, such as ABC COO (n = 16), TP53 loss (n = 13), DHITsig+ (n = 6), and CARD11 mutations associated with ibrutinib resistance (n = 3), were identified in 33 samples... Our results show the clinical utility and acceptable TAT of using a comprehensive WES and RNA-seq assay on a cohort of lymphoma patients. The produced BostonGene Tumor PortraitTM test reports included findings on significant alterations, LymphGen and LME subtypes, COOs, and potential clinical trial matches. These robust findings, coupled with the rapid TAT, demonstrate the feasibility of using integrated WES and RNA-seq to guide clinical decision-making in lymphoma patients.

Clinically significant findings, such as DHITsig+ (n = 4) and CARD11 mutations indicative of ibrutinib resistance (n = 3), were identified in 26 of the 39 patients ( Table 1), and an average of 8 clinical trials were identified for potential patient enrollment in each delivered report...This approach identified significant alterations and classified LBCL samples into previously reported lymphoma subtypes. The clinical reports included clinically relevant findings and matched clinical trials, demonstrating the feasibility of incorporating comprehensive molecular profiling in clinical practice for patients with lymphoma.

Functional studies demonstrated that CARD11 gain of function not only resulted in BCR independence but also directly increased the transcription of the antiapoptotic BCL2A1, leading to resistance against venetoclax and OAsIs combination...Consequently, MALT1 inhibition induced synergistic cell death in combination with BCL2 inhibition, irrespective of CARD11 mutational status, both in vitro and in vivo. Taken together our study identified mechanisms of resistance to targeted therapies and provided a novel strategy to overcome resistance in aggressive B-cell lymphoma.

He developed SPTCL-like lesions and membranoproliferative glomerulonephritis by age 2, treated successfully with cyclosporine...Autologous bone marrow transplant resulted in SPTCL remission despite persistent B cell lymphocytosis. These cases illuminate an unusual pathological manifestation for BENTA disease, suggesting that CARD11 GOF mutations can manifest in cutaneous CD4+ and CD8+ T cell malignancies.

The aaIPI staging combination with molecular biology markers is more conducive to accurately judging the prognosis of young DLBCL patients. TP53, POU2AF1 and CCND3 mutations predict worse survival in the patients with the aaIPI high-risk group.

QRICH1-deficient primary CD8+ T cells had increased proliferation and production of pro-inflammatory cytokines IFN-ɣ and TNF-α in response to ex vivo stimulation with anti-CD3/CD28, and QRICH1-deficient OT-1 CD8+ T cells also had increased cytokine production in response to antigen-specific stimulation with Ova peptide. Our findings reveal that QRICH1 negatively regulates T cell activation by modulating CARD11’s signaling output.

Our results reveal CARD11 as an important, cell-autonomous positive regulator of T, T and T cells. They highlight T cell-intrinsic effects of a GOF mutation in the CARD11 gene, which is recurrently mutated in T cell malignancies that are often aggressive and associated with variable clinical outcomes.

ETV6 and platelet-derived growth factor receptor (PDGFR)A/B gene mutations are supposed to be potential biomarkers for the prognosis of DLBCL patients via the statistical analysis of this small sample, and POD12 is also expected to be an effective endpoint for efficacy assessment.

CARD11(E626K) and HBZ cooperatively activate the non-canonical NF-κB pathway, IRF4 targets, BATF3/IRF4/HBZ transcriptional network, MYC targets, and E2F targets. Most KEGG and HALLMARK gene sets enriched in acute-type ATL are also enriched in double transgenic mice, indicating that these genes cooperatively contribute to ATL development.