PXD055845

PXD055845 is an original dataset announced via ProteomeXchange.

Title	Oncogenic and microenvironmental signals drive cell type-specific apoptosis resistance in juvenile myelomonocytic leukemia
Description	Juvenile myelomonocytic leukemia (JMML) is caused by constitutively activated RAS signalling and is characterized by increased proliferation and predominant myelomonocytic differentiation of hematopoietic cells. Using Mx-Cre;PTPN11D61Y mice, which reflect human JMML, we show that RAS pathway activation affects apoptosis signalling through cell type-dependent regulation of BCL-2 family members. Apoptosis resistance observed in monocytes and granulocytes was mediated by overexpression of the anti-apoptotic and down-regulation of the pro-apoptotic members of the BCL-2 family. Two anti-apoptotic proteins, BCL-XL and MCL-1, were directly regulated by the oncogenic RAS signalling but in addition were influenced by microenvironmental signals. While BCL-XL and BCL-2 were required for the survival of monocytes, MCL-1 was essential for neutrophils. Interestingly, stem and progenitor cells expressing the oncogenic PTPN11 mutant did not display any increased apoptosis resistance. BCL-XL inhibition was the most effective in killing myeloid cells in vitro but was not sufficient to completely resolve myeloproliferation in vivo.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_02:50:12.514.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Julia Mergner
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-13 04:52:25	ID requested
⏵ 1	2025-05-07 02:50:13	announced

10.1038/s41419-025-07479-2;

Koleci N, Wu Y, Wehner NA, Rajak J, Mittapalli VR, Mergner J, Xiao H, Wang J, Wahl M, Bohler S, Aumann K, H, ä, cker G, Ramamoorthy S, Boerries M, Kirschnek S, Erlacher M, Oncogenic and microenvironmental signals drive cell type specific apoptosis resistance in juvenile myelomonocytic leukemia. Cell Death Dis, 16(1):165(2025) [pubmed]

submitter keyword: PTPN11, BCL2, JMML, apoptosis, BCL-XL,Juvenile monocytic leukemia, MCL-1, extrinsic and intrinsic SHP2 signalling, SHP2

Julia Mergner
contact affiliation	Bavarian Center for Biomolecular Mass Spectrometry at Klinikum rechts der Isar (BayBioMS@MRI), TUM School of Medicine and Health, Technical University of Munich (TUM), 81675 München, Germany
contact email	julia.mergner@tum.de
lab head
Julia Mergner
contact affiliation	Chair of Proteomics and Bioanalytics, TU Munich
contact email	julia.mergner@tum.de
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/2025/05/PXD055845

PRIDE project URI

• PRIDE
  1. PXD055845
     1. Label: PRIDE project
     2. Name: Oncogenic and microenvironmental signals drive cell type-specific apoptosis resistance in juvenile myelomonocytic leukemia