PXD069537

PXD069537 is an original dataset announced via ProteomeXchange.

Title	Acute Myeloid Leukemia: a key role of DGKα and DGKζ in cell viability.
Description	Acute myeloid leukemia (AML) is a heterogeneous disease presenting a relevant unmeet clinical need for new therapeutic drugs. We and others reported increased expression of various diacylglycerol kinases (DGK) in AML. Inhere we study the effect of ritanserin, a DGKα specific inhibitor and DGKζ-IN4 / BAY 2965501, DGKζ specific inhibitors, on a panel of AML cell models. We also compared the effects observed with isoform specific silencing and finally explored the effect of those drugs on THP-1 cell proteome. We report that inhibitor sensitivity deeply varies among cell models, and it is not related to the level of target DGK isoform expression. Similarly, some cell lines are sensitive to DGKα silencing (HEL), some to DGKζ silencing (HL-60), while some are resistant to both (THP-1 and K562). Mechanistically, ritanserin deeply affects THP-1 proteome downregulating a significant fraction of proteins, while BAY 2965501 affects a reduced and distinct protein set, indicating distinct mechanisms of action. Those results suggest that targeting AML by DGK isoform specific inhibitors is possible but will require suitable markers for patient stratification.
HostingRepository	PRIDE
AnnounceDate	2025-11-24
AnnouncementXML	Submission_2025-11-23_16:21:26.873.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marcello Manfredi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-16 11:36:06	ID requested
⏵ 1	2025-11-23 16:21:28	announced

10.3390/cells14211721;

Gorla E, Cartella MC, Borghetti E, Lovati G, Racca L, Gravina T, Biazzo G, Bonello G, Malacarne V, De Giorgis V, Cor, à D, Manfredi M, Massarotti A, Graziani A, Baldanzi G, in Cell Viability. Cells, 14(21):(2025) [pubmed]

submitter keyword: Acute Myeloid Leukemia, Diacylglycerol kinases, Ritanserin, Proteome

Marcello Manfredi
contact affiliation	Prof. Marcello Manfredi PhD Biological Mass Spectrometry Lab Department of Translational Medicine (DiMeT) Center for Translational Research on Autoimmune & Allergic Diseases - CAAD University of Piemonte Orientale Corso Trieste 15/A, 28100, Novara, Italy
contact email	marcello.manfredi@med.uniupo.it
lab head
Marcello Manfredi
contact affiliation	University of Piemonte Orientale
contact email	marcello.manfredi@med.uniupo.it
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/2025/11/PXD069537

PRIDE project URI

• PRIDE
  1. PXD069537
     1. Label: PRIDE project
     2. Name: Acute Myeloid Leukemia: a key role of DGKα and DGKζ in cell viability.