ArticleCancer discovery2022
BCL10 Mutations Define Distinct Dependencies Guiding Precision Therapy for DLBCL.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 20 citations in OpenAlex.
- Molecular Pathogenesis and Therapeutic Response of Diffuse Large B Cell Lymphoma Genetic Subtypes.Annual review of cancer biology · 2026Article
- Therapeutic targeting of MALT1 in oncology: Mechanism, inhibitor development, and clinical prospects.Journal of cell communication and signaling · 2026Review
- T follicular helper cells transiently unlock a plasticity state in germinal centre B cells during the humoral immune response.Nature cell biology · 2026Article
- Analysis and Interpretation of Somatic NMD-Escaping Variants in Oncogenes and Dual-Function Genes across Adult and Pediatric Cancer Cohorts.medRxiv : the preprint server for health sciences · 2025Article
- Emodin Alleviates Sepsis-Induced Multiorgan Damage by Inhibiting NETosis through Targeting Neutrophils BCL-10.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Audit of B-cell cancer genes.Blood advances · 2025Review
- A small-molecule inhibitor of BCL10-MALT1 interaction abrogates progression of diffuse large B cell lymphoma.The Journal of clinical investigation · 2025Article
- A structural atlas of death domain fold proteins reveals their versatile roles in biology and function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Bruton's tyrosine kinase inhibition re-sensitizes multidrug-resistant DLBCL tumors driven by BCL10 gain-of-function mutants to venetoclax.Blood cancer journal · 2025Article
- Strategies for CRISPR-based knock-ins in primary human B cells and lymphoma cell lines.Frontiers in immunology · 2025Review
- Biomarker potential of nuclear Nrf2 activation in the ABC subtype of diffuse large B‑cell lymphoma.Oncology letters · 2025Article
- Infiltrating treg reprogramming in the tumor immune microenvironment and its optimization for immunotherapy.Biomarker research · 2024Review
- First-in-class inhibitor of HSP110 blocks BCR activation through SYK phosphorylation in diffuse large B-cell lymphoma.Leukemia · 2024Article
- Inhibition of MALT1 and BCL2 Induces Synergistic Antitumor Activity in Models of B-Cell Lymphoma.Molecular cancer therapeutics · 2024Article
- Profiling the activity of the para-caspase MALT1 in B-cell acute lymphoblastic leukemia for potential targeted therapeutic application.Haematologica · 2024Article
- TRAF3 loss-of-function reveals the noncanonical NF-κB pathway as a therapeutic target in diffuse large B cell lymphoma.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- ARID1A orchestrates SWI/SNF-mediated sequential binding of transcription factors with ARID1A loss driving pre-memory B cell fate and lymphomagenesis.Cancer cell · 2024Article
- Oncogene-induced MALT1 protease activity drives posttranscriptional gene expression in malignant lymphomas.Blood · 2023Article
- BTG1 inactivation drives lymphomagenesis and promotes lymphoma dissemination through activation of BCAR1.Blood · 2023Article
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Authors and funding
19 authors at 7 institutions in 3 countries.
Funding
Abstract
Activated B cell-like diffuse large B-cell lymphomas (ABC-DLBCL) have unfavorable outcomes and chronic activation of CARD11-BCL10-MALT1 (CBM) signal amplification complexes that form due to polymerization of BCL10 subunits, which is affected by recurrent somatic mutations in ABC-DLBCLs. Herein, we show that BCL10 mutants fall into at least two functionally distinct classes: missense mutations of the BCL10 CARD domain and truncation of its C-terminal tail. Truncating mutations abrogated a motif through which MALT1 inhibits BCL10 polymerization, trapping MALT1 in its activated filament-bound state. CARD missense mutations enhanced BCL10 filament formation, forming glutamine network structures that stabilize BCL10 filaments. Mutant forms of BCL10 were less dependent on upstream CARD11 activation and thus manifested resistance to BTK inhibitors, whereas BCL10 truncating but not CARD mutants were hypersensitive to MALT1 inhibitors. Therefore, BCL10 mutations are potential biomarkers for BTK inhibitor resistance in ABC-DLBCL, and further precision can be achieved by selecting therapy based on specific biochemical effects of distinct mutation classes. SIGNIFICANCE: ABC-DLBCLs feature frequent mutations of signaling mediators that converge on the CBM complex. We use structure-function approaches to reveal that BCL10 mutations fall into two distinct biochemical classes. Both classes confer resistance to BTK inhibitors, whereas BCL10 truncations confer hyperresponsiveness to MALT1 inhibitors, providing a road map for precision therapies in ABC-DLBCLs. See related commentary by Phelan and Oellerich, p. 1844. This article is highlighted in the In This Issue feature, p. 1825.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.