Alternative splicing of its 5'-UTR limits CD20 mRNA translation and enables resistance to CD20-directed immunotherapies.
Zhiwei AngLuca ParuzzoKatharina E HayerCarolin SchmidtManuel Torres-DizFeng XuUrvi ZankhariaYunlin ZhangSamantha SoldanSisi ZhengCatherine D FalkensteinJoseph P LoftusScarlett Y YangMukta AsnaniPatricia King SainosVinodh PillaiEmeline ChongMarilyn M LiSarah K TasianYoseph BarashPaul M LiebermanMarco RuellaStephen J SchusterAndrei Thomas-TikhonenkoPublished in: bioRxiv : the preprint server for biology (2023)
We discovered that in normal and malignant B-cells, CD20 mRNA is alternatively spliced to generate four distinct 5'-UTRs, including the longer translation-deficient V1 variant. Cells predominantly expressing V1 were still sensitive to CD20-targeting chimeric antigen receptor T-cells. However, they were resistant to the bispecific anti-CD3/CD20 antibody mosunetuzumab, and the shift to V1 were observed in CD20-negative post-mosunetuzumab relapses of follicular lymphoma.
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