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PXD021265-1

PXD021265 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteomic profiling reveals CDK6 upregulation as a targetable resistance mechanism for lenalidomide in multiple myeloma
DescriptionThe immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide are highly effective treatments for multiple myeloma. However, virtually all patients eventually relapse due to acquired drug resistance with resistance-causing genetic alterations being found only in a small subset of cases. Here, we performed integrated global quantitative tandem mass tag (TMT)-based proteomic and phosphoproteomic analyses and RNA sequencing in five paired pre-treatment and relapse samples from multiple myeloma patients to investigate non-genetic resistance mechanisms. These analyses revealed a CDK6-governed protein resistance signature that includes myeloma high-risk factors such as TRIP13 and RRM1. Overexpression of CDK6 in multiple myeloma cell lines reduced sensitivity to IMiDs while CDK6 inhibition by palbociclib or CDK6 degradation by proteolysis targeting chimeras (PROTACs) is highly synergistic with IMiDs in vitro and in vivo. In conclusion, we found upregulation of CDK6 to cause lenalidomide resistance in multiple myeloma that can be overcome by pharmacological intervention.
HostingRepositoryPRIDE
AnnounceDate2021-12-17
AnnouncementXMLSubmission_2021-12-17_09:06:11.514.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEvelyn Ramberger
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF-X
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-09-02 01:11:43ID requested
12021-12-17 09:06:11announced
Publication List
Dataset with its publication pending
Keyword List
ProteomeXchange project tag: Human Proteome Project
submitter keyword: multiple myeloma, LC-MS, TMT, CDK6
Contact List
Philipp Mertins
contact affiliationProteomics Platform, Max Delbrück Center for Molecular Medicine Berlin
contact emailPhilipp.Mertins@mdc-berlin.de
lab head
Evelyn Ramberger
contact affiliationMax Delbrück Center for Molecular Medicine, Berlin
contact emailevelyn.ramberger@mdc-berlin.de
dataset submitter
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Dataset FTP location
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