ArticleNature communications2022
High-throughput mutagenesis identifies mutations and RNA-binding proteins controlling CD19 splicing and CART-19 therapy resistance.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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Who cites it
45 citing papers in PubMed, 55 citations in OpenAlex.
- RHOA Deletion Downregulates CD19 and Promotes Dysfunctional Immune Microenvironments in CAR-T Resistant Large B-cell Lymphomas.Blood cancer discovery · 2026Article
- Tisa-cel and axi-cel CAR structure influences the development of resistance to CD19-CAR-T therapy.Leukemia · 2026Article
- Review
- Scaled Multidimensional Assays of Variant Effect Identify Sequence-Function Relationships in Hypertrophic Cardiomyopathy.Circulation · 2026Article
- Article
- Coordinated alternative splicing decisions via stepwise exon definition.Nucleic acids research · 2026Article
- RNA-binding proteins and ribonucleoproteins as determinants of immunity.Nature reviews. Immunology · 2026Review
- Mechanistic insights and clinical implications of RNA-binding proteins in prostate cancer.Discover oncology · 2026Review
- The race between 4-1BB- and CD28-based CD19 CAR-T products in the therapy of B-cell malignancies.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Integrating new and "old" cellular therapies in the evolving landscape of relapsed or refractory large B-cell lymphoma.Frontiers in oncology · 2026Review
- ThreeFrontiers in immunology · 2026Article
- IFNγ-induced antigen loss in chimeric antigen receptor-T cell therapy.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
- CD19-negative relapse after CAR-T cell therapy: mechanisms of antigen escape and lineage switch.Frontiers in immunology · 2026Review
- CD19 exon 2 skipping is a potential prognostic correlate of anti-CD19 CAR-T therapy relapse.Frontiers in molecular medicine · 2026Article
- Mechanistic basis and therapeutic modulation of T cell fitness to enhance CAR-T cell efficacy in hematological malignancies.Frontiers in immunology · 2026Review
- Research progress on resistance mechanisms to CAR-T cell therapy in diffuse large B-cell lymphoma.Frontiers in oncology · 2026Review
- Alternative Splicing-Mediated Resistance to Antibody-Based Therapies: Mechanisms and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Widespread prevalence of CD19 exon 5-6 skipping in primary pediatric B-Cell acute lymphoblastic leukemia patients.Molecular and cellular pediatrics · 2025Article
- Massively parallel assay of human splice variants reveals cis-regulatory drivers of disease-associated and cell type-specific splicing regulation.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
Abstract
Following CART-19 immunotherapy for B-cell acute lymphoblastic leukaemia (B-ALL), many patients relapse due to loss of the cognate CD19 epitope. Since epitope loss can be caused by aberrant CD19 exon 2 processing, we herein investigate the regulatory code that controls CD19 splicing. We combine high-throughput mutagenesis with mathematical modelling to quantitatively disentangle the effects of all mutations in the region comprising CD19 exons 1-3. Thereupon, we identify ~200 single point mutations that alter CD19 splicing and thus could predispose B-ALL patients to developing CART-19 resistance. Furthermore, we report almost 100 previously unknown splice isoforms that emerge from cryptic splice sites and likely encode non-functional CD19 proteins. We further identify cis-regulatory elements and trans-acting RNA-binding proteins that control CD19 splicing (e.g., PTBP1 and SF3B4) and validate that loss of these factors leads to pervasive CD19 mis-splicing. Our dataset represents a comprehensive resource for identifying predictive biomarkers for CART-19 therapy.
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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.