PXD021265-1

PXD021265 is an original dataset announced via ProteomeXchange.

Title	Proteomic profiling reveals CDK6 upregulation as a targetable resistance mechanism for lenalidomide in multiple myeloma
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2021-12-17
AnnouncementXML	Submission_2021-12-17_09:06:11.514.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Evelyn Ramberger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-02 01:11:43	ID requested
⏵ 1	2021-12-17 09:06:11	announced

Dataset with its publication pending

ProteomeXchange project tag: Human Proteome Project

submitter keyword: multiple myeloma, LC-MS, TMT, CDK6

Philipp Mertins
contact affiliation	Proteomics Platform, Max Delbrück Center for Molecular Medicine Berlin
contact email	Philipp.Mertins@mdc-berlin.de
lab head
Evelyn Ramberger
contact affiliation	Max Delbrück Center for Molecular Medicine, Berlin
contact email	evelyn.ramberger@mdc-berlin.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021265
     1. Label: PRIDE project
     2. Name: Proteomic profiling reveals CDK6 upregulation as a targetable resistance mechanism for lenalidomide in multiple myeloma