PXD026293

PXD026293 is an original dataset announced via ProteomeXchange.

Title	Inhibition of NLRP3 enhances pro-apoptotic effects of FLT3 inhibition in AML
Description	FLT3 mutations occur in approximately 25% of all acute myeloid leukemia (AML) patients. While several FLT3 inhibitors have received FDA approval, their use is currently limited to combination therapies with chemotherapy, as resistance occurs, and efficacy decreases when the inhibitors are used alone. Given the highly heterogeneous nature of AML, there is an urgent need for novel targeted therapies that address the disease from multiple angles. Recent research has identified the NLRP3 inflammasome as a potential new driver in AML. Here, we investigated the efficacy of different NLRP3 inhibitors in targeting AML cells in vitro. Our findings reveal that NLRP3 inhibition induces cell cycle arrest as well as signs of senescence in multiple AML cell lines. In contrast, NLRP3 inhibition selectively induced apoptosis in FLT3 mutant AML cell lines, but not in FLT3 wild-type AML cells. Moreover, we show that NLRP3 inhibition impairs FLT3 signaling by reducing both FLT3 expression as well as downstream signaling in FLT3 mutant cells. A database analysis revealed a strong positive correlation between FLT3 and NLRP3 in cancer, which was particularly evident in AML patients. Strikingly, the simultaneous inhibition of NLRP3 and FLT3 markedly enhanced apoptosis in FLT3-ITD mutant AML cells, but not in FLT3 wild-type cells. In summary, this study reveals a promising combined therapeutic strategy specifically targeting NLRP3/FLT3-ITD positive AML blasts in vitro, highlighting a potential new avenue for AML treatment.
HostingRepository	PRIDE
AnnounceDate	2025-02-06
AnnouncementXML	Submission_2025-02-06_07:47:20.270.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Constantin Blöchl
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-26 09:10:13	ID requested
⏵ 1	2025-02-06 07:47:21	announced

10.1186/s12964-025-02046-w;

Sieberer H, Luciano M, Amend D, Bl, ö, chl C, Eglseer A, Steinkellner A, Rieser S, Andosch A, Steiner P, Hummer L, Krenn PW, Dang HH, Huber CG, Aberger F, Neuper T, Horejs-Hoeck J, Inhibition of NLRP3 enhances pro-apoptotic effects of FLT3 inhibition in AML. Cell Commun Signal, 23(1):53(2025) [pubmed]

submitter keyword: Acute Myeloid Leukemia, EiF2α, NLRP3

Christian G. Huber
contact affiliation	Department of Biosciences and Medical Biology, Paris-Lodron University Salzburg, 5020 Salzburg, Austria
contact email	c.huber@sbg.ac.at
lab head
Constantin Blöchl
contact affiliation	Department of Biosciences, University of Salzburg
contact email	constantin.bloechl@sbg.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/2025/02/PXD026293

PRIDE project URI

• PRIDE
  1. PXD026293
     1. Label: PRIDE project
     2. Name: Inhibition of NLRP3 enhances pro-apoptotic effects of FLT3 inhibition in AML