ArticleBlood2023
Alternative splicing of its 5'-UTR limits CD20 mRNA translation and enables resistance to CD20-directed immunotherapies.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 40 citations in OpenAlex.
- Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial.Nature medicine · 2024Trial
- Functional analysis ofMolecular therapy. Nucleic acids · 2026Article
- Bispecific Antibody-Based Combination Therapies for B-Cell Lymphomas: Current Evidence and Future Perspectives.International journal of cancer · 2026Review
- CD20 re-emergence in a patient with diffuse large B-cell lymphoma who experienced a CD20-negative relapse after glofitamab treatment.Haematologica · 2026Article
- Therapeutic upregulation of gene expression in inherited cardiomyopathies from current approaches to future directions.Nature cardiovascular research · 2026Review
- Characterization of JNJ-80948543 a novel CD79bxCD20xCD3 trispecific antibody for B-cell non-Hodgkin lymphoma.Haematologica · 2026Article
- Cancer cell-selective ectopic expression of CD20 as an antigen enables rituximab repurposing for solid tumour immunotherapy.Clinical and translational medicine · 2026Article
- An upstream open reading frame represses translation of the neuronal potassium channel KCNQ2.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Toward Precision Oral Medicine in Pemphigus Vulgaris: A Conceptual AI Framework for Rituximab Response Prediction.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Interpretable and scalable spatial gene set activity analysis with GESSO uncovers functional tissue architecture.bioRxiv : the preprint server for biology · 2026Article
- An SLCO2B1 mRNA Isoform Acts as a Noncoding RNA to Drive Cancer Progression by Triggering Protein Biosynthesis.Cancer research · 2026Article
- The emerging roles of alternative splicing in modulating tumor immune responses and immunotherapies.Cell death and differentiation · 2026Review
- Nanopore direct RNA sequencing and the epitranscriptome: Advances in mapping native RNA landscapes.iMeta · 2026Review
- Molecular features of response and resistance to glofitamab, a T-cell engager for treatment of large B-cell lymphoma.Blood advances · 2026Article
- Molecular Mechanisms of Resistance to Bispecific Antibodies in Diffuse Large B-Cell Lymphoma.Cells · 2026Review
- Targeted BDNF upregulation via upstream open reading frame disruption.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Alternative splicing in cancer drug resistance: Mechanisms and therapeutic prospects (Review).Oncology reports · 2026Review
- Case Report: Diagnostic pitfall and biomarker-guided therapy in CD20-negative Epstein-Barr virus-positive diffuse large B-cell lymphoma.Frontiers in immunology · 2026Article
- Dual-trigger model of CD20 escape: NONO regulation and cryptic splicing induced by transcript overload in pediatric B-ALL.Frontiers in immunology · 2026Article
- Alternative Splicing-Mediated Resistance to Antibody-Based Therapies: Mechanisms and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
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Authors and funding
24 authors at 3 institutions in 1 country.
Funding
Abstract
Aberrant skipping of coding exons in CD19 and CD22 compromises the response to immunotherapy in B-cell malignancies. Here, we showed that the MS4A1 gene encoding human CD20 also produces several messenger RNA (mRNA) isoforms with distinct 5' untranslated regions. Four variants (V1-4) were detected using RNA sequencing (RNA-seq) at distinct stages of normal B-cell differentiation and B-lymphoid malignancies, with V1 and V3 being the most abundant. During B-cell activation and Epstein-Barr virus infection, redirection of splicing from V1 to V3 coincided with increased CD20 positivity. Similarly, in diffuse large B-cell lymphoma, only V3, but not V1, correlated with CD20 protein levels, suggesting that V1 might be translation-deficient. Indeed, the longer V1 isoform contained upstream open reading frames and a stem-loop structure, which cooperatively inhibited polysome recruitment. By modulating CD20 isoforms with splice-switching morpholino oligomers, we enhanced CD20 expression and anti-CD20 antibody rituximab-mediated cytotoxicity in a panel of B-cell lines. Furthermore, reconstitution of CD20-knockout cells with V3 mRNA led to the recovery of CD20 positivity, whereas V1-reconstituted cells had undetectable levels of CD20 protein. Surprisingly, in vitro CD20-directed chimeric antigen receptor T cells were able to kill both V3- and V1-expressing cells, but the bispecific T-cell engager mosunetuzumab was only effective against V3-expressing cells. To determine whether CD20 splicing is involved in immunotherapy resistance, we performed RNA-seq on 4 postmosunetuzumab follicular lymphoma relapses and discovered that in 2 of them, the downregulation of CD20 was accompanied by a V3-to-V1 shift. Thus, splicing-mediated mechanisms of epitope loss extend to CD20-directed immunotherapies.
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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.