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PXD043670

PXD043670 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMolecular Determinants of Sensitivity to Polatuzumab Vedotin in Diffuse Large B Cell Lymphoma
DescriptionPolatuzumab Vedotin (Pola-V) is an antibody-drug conjugate directed to the CD79B subunit of the B cell receptor (BCR). When combined with conventional immunochemotherapy, Pola-V improves outcomes in DLBCL. To identify molecular determinants of sensitivity to Pola-V, we used CRISPR-Cas9 screening for genes that modulated the toxicity of Pola-V for lymphomas or the surface expression of its target, CD79B. Our results reveal a striking impact of CD79B glycosylation on Pola-V epitope availability on the lymphoma cell surface and on Pola-V toxicity. Genetic, pharmacological, and enzymatic approaches that remove terminal sialic acid residues from N-linked glycans enhanced lymphoma killing by Pola-V. Pola-V toxicity was also modulated by KLHL6, a ubiquitin ligase that targets CD79B for degradation in normal and malignant germinal center B cells, explaining its recurrent inactivation in germinal center-derived lymphomas. Our findings suggest precision medicine strategies to optimize Pola-V as a lymphoma therapeutic.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:49:22.656.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEvangelia Papachristou
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmethylthiolated residue; monohydroxylated residue; deamidated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-07-11 04:51:10ID requested
12024-07-12 02:04:20announced
22024-10-22 06:49:23announced2024-10-22: Updated project metadata.
Publication List
10.1158/2159-8290.CD-23-0802;
Keyword List
submitter keyword: ubiquitylation, glycosylation,B cell receptor, KLHL6
Contact List
Daniel J. Hodson
contact affiliation2. Wellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
contact emaildjh1002@cam.ac.uk
lab head
Evangelia Papachristou
contact affiliationSenior Scientific Assistant
contact emailEva.Papachristou@cruk.cam.ac.uk
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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