PXD016839

PXD016839 is an original dataset announced via ProteomeXchange.

Title	Antileukemic activity of the VPS34-IN1 inhibitor in acute myeloid leukemia
Description	Acute myeloid leukemia (AML) is an aggressive disease with a poor prognosis. Vacuolar protein sorting 34 (VPS34) is a member of the phosphatidylinositol-3-kinase lipid kinase family that controls the canonical autophagy pathway and vesicular trafficking. Using a recently developed specific inhibitor (VPS34-IN1), we found that a VPS34 block induces apoptosis in AML cells but not in normal CD34+ hematopoietic cells. Complete and acute inhibition of VPS34 was required for the anti-leukemic activity of VPS34-IN1. This inhibitor also has pleiotropic effects against various cellular functions related to class III PI3K in AML cells that may explain their survival impairment. VPS34-IN1 inhibits basal and L-asparaginase-induced autophagy in AML cells. A synergistic cell death activity of this drug was also demonstrated. VPS34-IN1 was additionally found to impair vesicular trafficking and mTORC1 signaling. From an unbiased approach based on phosphoproteomic analysis, we identified that VPS34-IN1 specifically inhibits STAT5 phosphorylation downstream of FLT3-ITD signaling in AML. The identification of the mechanisms controlling FLT3-ITD signaling by VPS34 represents an important insight into the oncogenesis of AML and could lead to new therapeutic strategies.
HostingRepository	PRIDE
AnnounceDate	2020-11-11
AnnouncementXML	Submission_2020-11-11_09:02:40.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	François GUILLONNEAU
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-19 05:48:34	ID requested
⏵ 1	2020-11-11 09:02:40	announced

Meunier G, Birsen R, Cazelles C, Belhadj M, Cantero-Aguilar L, Kosmider O, Fontenay M, Azar N, Mayeux P, Chapuis N, Tamburini J, Bouscary D, Antileukemic activity of the VPS34-IN1 inhibitor in acute myeloid leukemia. Oncogenesis, 9(10):94(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: Orbitrap fusion, human MOLM-14 cells, VPS34, VPS34-IN1, AML, L-asparaginase, autophagy

Didier Bouscary
contact affiliation	Service d’hématologie Clinique et biologique, Hôpital Cochin, Paris. Université de Paris, Institut Cochin, Inserm U1016, Département Développement, Reproduction, Cancer, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104 Paris
contact email	didier.bouscary@aphp.fr
lab head
François GUILLONNEAU
contact affiliation	3P5 Université Paris Descartes
contact email	francois.guillonneau@parisdescartes.fr
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/2020/11/PXD016839

PRIDE project URI

• PRIDE
  1. PXD016839
     1. Label: PRIDE project
     2. Name: Antileukemic activity of the VPS34-IN1 inhibitor in acute myeloid leukemia