Nature Communications (Sep 2022)
High-throughput mutagenesis identifies mutations and RNA-binding proteins controlling CD19 splicing and CART-19 therapy resistance
- Mariela Cortés-López,
- Laura Schulz,
- Mihaela Enculescu,
- Claudia Paret,
- Bea Spiekermann,
- Mathieu Quesnel-Vallières,
- Manuel Torres-Diz,
- Sebastian Unic,
- Anke Busch,
- Anna Orekhova,
- Monika Kuban,
- Mikhail Mesitov,
- Miriam M. Mulorz,
- Rawan Shraim,
- Fridolin Kielisch,
- Jörg Faber,
- Yoseph Barash,
- Andrei Thomas-Tikhonenko,
- Kathi Zarnack,
- Stefan Legewie,
- Julian König
Affiliations
- Mariela Cortés-López
- Institute of Molecular Biology (IMB)
- Laura Schulz
- Institute of Molecular Biology (IMB)
- Mihaela Enculescu
- Institute of Molecular Biology (IMB)
- Claudia Paret
- Department of Pediatric Hematology/Oncology, Center for Pediatric and Adolescent Medicine, University Medical Center of the Johannes Gutenberg University Mainz
- Bea Spiekermann
- Institute of Molecular Biology (IMB)
- Mathieu Quesnel-Vallières
- Department of Genetics, Perelman School of Medicine at the University of Pennsylvania
- Manuel Torres-Diz
- Division of Cancer Pathobiology, Children’s Hospital of Philadelphia
- Sebastian Unic
- Department of Systems Biology, Institute for Biomedical Genetics (IBMG), University of Stuttgart
- Anke Busch
- Institute of Molecular Biology (IMB)
- Anna Orekhova
- Institute of Molecular Biology (IMB)
- Monika Kuban
- Department of Systems Biology, Institute for Biomedical Genetics (IBMG), University of Stuttgart
- Mikhail Mesitov
- Institute of Molecular Biology (IMB)
- Miriam M. Mulorz
- Institute of Molecular Biology (IMB)
- Rawan Shraim
- Division of Cancer Pathobiology, Children’s Hospital of Philadelphia
- Fridolin Kielisch
- Institute of Molecular Biology (IMB)
- Jörg Faber
- Department of Pediatric Hematology/Oncology, Center for Pediatric and Adolescent Medicine, University Medical Center of the Johannes Gutenberg University Mainz
- Yoseph Barash
- Department of Genetics, Perelman School of Medicine at the University of Pennsylvania
- Andrei Thomas-Tikhonenko
- Division of Cancer Pathobiology, Children’s Hospital of Philadelphia
- Kathi Zarnack
- Buchmann Institute for Molecular Life Sciences (BMLS)
- Stefan Legewie
- Institute of Molecular Biology (IMB)
- Julian König
- Institute of Molecular Biology (IMB)
- DOI
- https://doi.org/10.1038/s41467-022-31818-y
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 17
Abstract
Multiple alternative splicing events in CD19 mRNA have been associated with resistance/relapse to CD19 CAR-T therapy in patients with B cell malignancies. Here, by combining patient data and a high-throughput mutagenesis screen, the authors identify single point mutations and RNA-binding proteins that can control CD19 splicing and be associated with CD19 CAR-T therapy resistance.
