PXD073478-1

PXD073478 is an original dataset announced via ProteomeXchange.

Title	Subcellular proteomics of FLT3-ITD cells
Description	In acute myeloid leukemia (AML), the insertion site of internal tandem duplications (ITDs) within the FLT3 gene critically determines the sensitivity to tyrosine kinase inhibitors (TKIs). Despite recent advances, patients harboring ITDs in the tyrosine kinase domain (TKD) still lack effective therapeutic options. To elucidate the molecular basis underlying the differential TKI sensitivity of FLT3-ITD cells, we integrated high-resolution mass spectrometry–based (phospho)proteomics with subcellular fractionation. Our analysis revealed that midostaurin induces the subcellular redistribution of approximately 2500 proteins involved in crucial biological processes, including cell cycle control, autophagy, and metabolism. Functional analyses further demonstrated that the ITD insertion site determines the autophagy response to midostaurin and modulates mitochondrial metabolism, influencing organelle architecture and ATP production, even at steady state. Importantly, by integrating subcellular proteomic dataset with functional metabolic assays, we uncovered a lipid-dependent vulnerability of FLT3-ITD cells: lipid restriction enhances FLT3 trafficking to the plasma membrane, and markedly reduces cell viability, restoring midostaurin sensitivity of resistant FLT3-ITD cells. Together, our findings reveal that the FLT3-ITD insertion site orchestrates a coordinated remodeling of subcellular protein organization, autophagy, and metabolism, and identify lipid-mediated control of FLT3 compartmentalization as a therapeutically actionable mechanism to overcome TKI resistance in FLT3-ITD AML.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-07_09:13:38.060.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Francesca Sacco
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-23 13:42:22	ID requested
⏵ 1	2026-09-07 09:13:39	announced

10.1038/s41375-026-03000-6;

Bica V, Pacil, è AF, Boettcher M, Marano V, Marabitti V, Nazio F, Cortese M, Fischer T, Perfetto L, Mougiakakos D, Massacci G, Sacco F, Organelle proteomics reveals novel metabolic vulnerabilities in FLT3-ITD cells. Leukemia, 40(8):1657-1667(2026) [pubmed]

submitter keyword: AML, FLT3-ITD, fractions

Francesca Sacco
contact affiliation	Dept. of Bioloy, 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/2026/09/PXD073478

PRIDE project URI

• PRIDE
  1. PXD073478
     1. Label: PRIDE project
     2. Name: Subcellular proteomics of FLT3-ITD cells