Article
High-throughput mutagenesis identifies mutations and RNA-binding proteins controlling CD19 splicing and CART-19 therapy resistance.
Nature communications - 22 Sept 2022
Cortés-López Mariela, Schulz Laura, Enculescu Mihaela, Paret Claudia, Spiekermann Bea, Quesnel-Vallières Mathieu, Torres-Diz Manuel, Unic Sebastian, Busch Anke, Orekhova Anna, Kuban Monika, Mesitov Mikhail, Mulorz Miriam M, Shraim Rawan, Kielisch Fridolin, Faber Jörg, Barash Yoseph, Thomas-Tikhonenko Andrei, Zarnack Kathi, Legewie Stefan, König Julian
Abstract excerpt
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...
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