PXD061404

PXD061404 is an original dataset announced via ProteomeXchange.

Title	In-Depth Proteomics Reveals Selective EV Protein Sorting and Pathway Perturbation in AML upon Synergistic FLT3 and Hedgehog Pathway Inhibition
Description	Acute myeloid leukemia (AML) is an aggressive cancer mainly affecting bone marrow and blood with a high relapse incidence and mortality rate. Approximately one third of AML patients carry an fms-like tyrosine kinase 3 (FLT3) mutation, which is often associated with GLI expression and Hedgehog signaling, leading to tumor proliferation. AML cells shape their microenvironment into a leukemia-permissive space by releasing extracellular vesicles (EVs). EVs can transfer chemoresistance and thereby play an important role in refractory and relapsing diseases. Here, we discovered a synergistic effect of a combined treatment with the FLT3 inhibitor Crenolanib and the Hedgehog pathway inhibitor HPI-1 in the AML cell lines MOLM-14 and MV4-11. In-depth comparative proteomics revealed alterations in the cellular and the EV proteome upon single or combined inhibition of FLT3 and GLI, highlighting affected pathways. By comparing the cellular and EV proteomes, we report that transport of ribosomal proteins such as RPS26 and RPL27A and ErbB pathway members such as GAB1, GRB2 and SHC1 to EVs is selectively avoided upon treatment with Crenolanib. Ribosomal and ErbB signaling pathway proteins may play an important role in microenvironmental modulation by EVs, and Crenolanib treatment potentially acts by interfering with leukemia niche formation.
HostingRepository	PRIDE
AnnounceDate	2025-09-29
AnnouncementXML	Submission_2025-09-28_17:23:35.328.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gabriele Blümel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-03 08:21:18	ID requested
⏵ 1	2025-09-28 17:23:36	announced

Bl, ö, chl C, Bl, ü, mel G, Wolf M, Regl C, Binder HM, Tesanovic S, Lankes D, Maeding N, Krenn PW, Strunk D, Aberger F, Huber CG, Selective EV Protein Sorting and Pathway Perturbation in AML Upon Synergistic FLT3 and Hedgehog Pathway Inhibition. J Extracell Vesicles, 14(9):e70163(2025) [pubmed]

10.1002/jev2.70163;

submitter keyword: HPI-1,Proteomics, ErbB signaling, EVs, Crenolanib, ribosomal proteins, AML

Christof Regl
contact affiliation	Department of Biosciences & Medical Biology, Paris Lodron University of Salzburg, Austria.
contact email	christof.regl@plus.ac.at
lab head
Gabriele Blümel
contact affiliation	Paris Lodron University, Salzburg
contact email	gabriele.bluemel@plus.ac.at
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/2025/09/PXD061404

PRIDE project URI

• PRIDE
  1. PXD061404
     1. Label: PRIDE project
     2. Name: In-Depth Proteomics Reveals Selective EV Protein Sorting and Pathway Perturbation in AML upon Synergistic FLT3 and Hedgehog Pathway Inhibition