PXD025507

PXD025507 is an original dataset announced via ProteomeXchange.

Title	Actinomycin targets NPM1c-primed mitochondria in AML
Description	Acute myeloid leukemia (AML) pathogenesis often involves a mutation in the NPM1 nucleolar chaperone, but the bases for its transforming properties and association with favorable outcome remain incompletely understood. Here we demonstrate that an oncogenic mutant form of NPM1 (NPM1c) hampers formation of PML nuclear bodies (NBs), key senescence effectors, and impairs mitochondrial function to drive an integrated stress response. Actinomycin D (ActD), an antibiotic with unambiguous clinical efficacy in relapsed/refractory NPM1c-AMLs, preferentially targets these primed mitochondria, activating cGAS signaling and boosting ROS production. The later restores PML NB formation to drive senescence of NPM1c-AMLs cells. Dual targeting of mitochondria by Venetoclax and ActD synergized for AML elimination. Our studies reveal a central role of mitochondria downstream of NPM1c and implicate a mitochondrial/ROS/PML/TP53 senescence pathway as a key effector of ActD-based, and possibly others, chemotherapies.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:52:21.102.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	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-20 23:11:38	ID requested
1	2021-12-17 06:43:10	announced
⏵ 2	2023-11-14 08:52:21	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: PML, LFQ, Actinomycin D, mitochondria,NPM1c, Qexactive, senescence

Hugues de Thé
contact affiliation	Collège de France, Oncologie Cellulaire et Moléculaire, PSL University, INSERM UMR 1050, CNRS UMR 7241, INSERM UMR 944, CNRS UMR 7212, Université de Paris, IRSL, Hôpital St. Louis Paris France
contact email	hugues.dethe@inserm.fr
lab head
François GUILLONNEAU
contact affiliation	ICO Angers
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/2021/12/PXD025507

PRIDE project URI

• PRIDE
  1. PXD025507
     1. Label: PRIDE project
     2. Name: Actinomycin targets NPM1c-primed mitochondria in AML