PXD056957-1

PXD056957 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomics reveals a crucial role of FLT3 in BCR::ABL1 independent resistant chronic myeloid leukemia
Description	BCR::ABL1 drives chronic myeloid leukemia (CML) pathology and treatment, as revealed by the success of tyrosine kinase inhibitor (TKI) therapy. However, additional poorly characterized molecular mechanisms, acting independently of BCR::ABL1, play crucial roles in CML, contributing to leukemic stem cells (LSCs) persistence, drug resistance and disease progression. Here, by combining high sensitive mass spectrometry (MS)-based phosphoproteomics with the SignalingProfiler pipeline, we obtained two signaling maps reporting the BCR::ABL1 dependent and independent pro-survival signalling mechanisms, respectively. Crucial oncogenic pathways were deregulated in resistant cells. To unbiasedly discover therapeutic vulnerabilities, we implemented the Druggability Score, a computational algorithm ranking proteins according to their inferred ability to kill resistant cells when suppressed. By this strategy, we identified a novel and unexpected role for FLT3 in BCR::ABL1 independent resistance. Remarkably, pharmacological suppression of FLT3 triggers death of both resistant cell lines and patients-derived LSCs. Finally, we propose midostaurin treatment as a therapeutic option to improve the clinical outcome of non responder patients and eradicate LSCs.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_04:14:04.956.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Francesca Sacco
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-18 10:53:20	ID requested
⏵ 1	2025-05-07 04:14:05	announced

Bica V, Venafra V, Massacci G, Graziosi S, Gualdi S, Minnella G, Sor, à F, Chiusolo P, Brunetti ME, Napolitano G, Breccia M, Mougiakakos D, B, ö, ttcher M, Fischer T, Perfetto L, Sacco F, A network-based approach to overcome BCR::ABL1-independent resistance in chronic myeloid leukemia. Cell Commun Signal, 23(1):179(2025) [pubmed]

10.1186/s12964-025-02185-0;

submitter keyword: Leukemia, FLT3

Francesca Sacco
contact affiliation	University of Rome Tor Vergata
contact email	francesca.sacco@uniroma2.it
lab head
Francesca Sacco
contact affiliation	University of Rome Tor Vergata
contact email	francesca.sacco@uniroma2.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/2025/05/PXD056957

PRIDE project URI

• PRIDE
  1. PXD056957
     1. Label: PRIDE project
     2. Name: Phosphoproteomics reveals a crucial role of FLT3 in BCR::ABL1 independent resistant chronic myeloid leukemia