PXD061362

PXD061362 is an original dataset announced via ProteomeXchange.

Title	Genetic or pharmacological inactivation of CREBBP sensitizes B-cell Acute Lymphoblastic Leukemia to Ferroptotic Cell Death upon BCL2 Inhibition
Description	Performing a targeted drug-screen in isogenic human cell lines, we idenTfied a number of small molecules that specifically targeted CREBBP-mutated B-ALL, with the most potent the BCL2-inhibitor Venetoclax. Of note, this acted through a non-canonical mechanism resulTng in ferroptoTc rather than apoptoTc cell death. CREBBP-mutated cell lines showed differences in cell- cycle, metabolism, lipid composiTon and response to oxidaTve stress, predisposing them to ferroptosis, which were further dysregulated upon acquisiTon of Venetoclax resistance. Lastly, small- molecule inhibiTon of CREBBP pharmacocopies CREBBP-mutaTon, sensiTzing B-ALL cells, regardless of genotype, to Venetoclax-induced ferroptosis in-vitro and in-vivo, providing a potential novel drug combination for broader clinical translation in B-ALL.
HostingRepository	PRIDE
AnnounceDate	2025-05-01
AnnouncementXML	Submission_2025-05-01_04:37:10.215.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dhoyazan Azazi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-02 13:50:49	ID requested
⏵ 1	2025-05-01 04:37:10	announced

10.1038/S41467-025-59531-6;

submitter keyword: Human, B-cell, Acute Lymphoblastic Leukemia, CREBBP, BCL2, ALL

Brian J.P. Huntly
contact affiliation	Department of Haematology, Cambridge Stem Cell Institute, Cambridge, UK Cambridge University Hospitals, Cambridge, UK
contact email	bjph2@cam.ac.uk
lab head
Dhoyazan Azazi
contact affiliation	Cambridge Stem Cell Institute Department of Haematology University of Cambridge
contact email	dmaa2@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/2025/05/PXD061362

PRIDE project URI

• PRIDE
  1. PXD061362
     1. Label: PRIDE project
     2. Name: Genetic or pharmacological inactivation of CREBBP sensitizes B-cell Acute Lymphoblastic Leukemia to Ferroptotic Cell Death upon BCL2 Inhibition