PXD043670-1

PXD043670 is an original dataset announced via ProteomeXchange.

Title	Molecular Determinants of Sensitivity to Polatuzumab Vedotin in Diffuse Large B Cell Lymphoma
Description	Polatuzumab 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.
HostingRepository	PRIDE
AnnounceDate	2024-07-12
AnnouncementXML	Submission_2024-07-12_02:04:20.241.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Evangelia Papachristou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; monohydroxylated residue; deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-11 04:51:10	ID requested
⏵ 1	2024-07-12 02:04:20	announced
2	2024-10-22 06:49:23	announced	2024-10-22: Updated project metadata.

10.1158/2159-8290.CD-23-0802;

submitter keyword: ubiquitylation, glycosylation,B cell receptor, KLHL6

Daniel J. Hodson
contact affiliation	2. Wellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
contact email	djh1002@cam.ac.uk
lab head
Evangelia Papachristou
contact affiliation	Senior Scientific Assistant
contact email	Eva.Papachristou@cruk.cam.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/07/PXD043670

PRIDE project URI

• PRIDE
  1. PXD043670
     1. Label: PRIDE project
     2. Name: Molecular Determinants of Sensitivity to Polatuzumab Vedotin in Diffuse Large B Cell Lymphoma