⮝ Full datasets listing

PXD063244-1

PXD063244 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleGPCR5D alterations provide proliferative advantage in multiple myeloma
DescriptionImmunotherapies targeting surface antigens have transformed the treatment landscape of multiple myeloma (MM), with GPRC5D emerging as a promising therapeutic target, although its physiological function remains undefined. Mono-allelic loss of GPRC5D is frequently observed in newly diagnosed MM patients, and the incidence of acquired GPRC5D alterations increases following exposure to GPRC5D-directed therapies. However, the functional consequences of both baseline mono-allelic and therapy-induced biallelic GPRC5D alterations remain poorly understood. In this study, we modeled various GPRC5D genetic alterations to investigate their impact on myeloma cell biology and responsiveness to GPRC5D-targeted immunotherapies. Our results demonstrate that mono-allelic GPRC5D loss reduces surface expression of the antigen and confers resistance to GPRC5D-directed therapies. Complete loss of GPRC5D induces transcriptional and phosphoproteomic reprogramming that promotes a proliferative phenotype and alters chemokine signaling. Clonal competition assays reveal that both functional and non-functional CAR-T cells preferentially select for GPRC5D-deficient cells. Collectively, our findings reveal that GPRC5D loss exerts a dual effect in MM by driving resistance to GPRC5D-targeted immunotherapies and enhancing tumor fitness through proliferative reprogramming.
HostingRepositoryMassIVE
AnnounceDate2026-02-11
AnnouncementXMLSubmission_2026-02-11_03:55:47.279.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJohanna Thurner
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListCarbamidomethyl; Oxidation; Acetyl; Phospho
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-04-23 06:17:27ID requested
12026-02-11 03:55:47announced
Publication List
no publication
Keyword List
submitter keyword: cancer, Multiple myeloma, Bottom-up proteomics, GPRC5D, Immunotherapies, Bispecific antibodies, DatasetType:Proteomics
Contact List
Bernhard Kuster
contact affiliationChair of proteomics and bioanalytics (Technical University of Munich)
contact emailkuster@tum.de
lab head
Johanna Thurner
contact affiliationTUM
contact emailjohanna.thurner@tum.de
dataset submitter
Full Dataset Link List
MassIVE dataset URI
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://massive-ftp.ucsd.edu/v09/MSV000097698/