PXD014708

PXD014708 is an original dataset announced via ProteomeXchange.

Title	Proteomic analysis of an induced pluripotent stem cell model reveals strategies to treat Juvenile Myelomonocytic Leukaemia
Description	Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm of early childhood with a poor survival rate thus there is a requirement for improved treatment strategies. Induced pluripotent stem cells offer the ability to model disease and develop new treatment strategies. JMML is frequently associated with mutations in PTPN11. Children with Noonan syndrome, a development disorder, have an increased incidence of JMML associated with specific germline mutations in PTPN11. We undertook a proteomic assessment of myeloid cells derived from induced pluripotent stem cells obtained from Noonan syndrome patients with PTPN11 mutations, either associated or not associated with increased incidence of JMML. We report that the proteomic perturbations induced by the leukaemia-associated PTPN11 mutations are associated with TP53 and NF-ĸb signalling. We have previously shown that MYC is involved in the differential gene expression observed in Noonan syndrome patients associated with increased incidence of JMML. Thus, we employed drugs to target these pathways and demonstrate differentential effects on clonogenic hematopoietic cells derived from Noonan syndrome patients whom develop JMML and those who do not. Further, we demonstrated these small molecular inhibitors, JQ1 and CBL0137, preferentially extinguish primitive haematopoietic cells from sporadic JMML patients as opposed to cells from healthy individuals.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:02:35.820.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bethany Geary
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iTRAQ8plex-116 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-23 05:48:13	ID requested
1	2019-10-30 02:35:55	announced
⏵ 2	2024-10-22 04:02:36	announced	2024-10-22: Updated project metadata.

10.1021/acs.jproteome.9b00495;

Pearson S, Guo B, Pierce A, Azadbakht N, Brazzatti JA, Patassini S, Mulero-Navarro S, Meyer S, Flotho C, Gelb BD, Whetton AD, Proteomic Analysis of an Induced Pluripotent Stem Cell Model Reveals Strategies to Treat Juvenile Myelomonocytic Leukemia. J Proteome Res, 19(1):194-203(2020) [pubmed]

submitter keyword: PTPN11, JQ1,Noonan syndrome, JMML, CBL0137

Tony Whetton
contact affiliation	University of Manchester
contact email	tony.whetton@manchester.ac.uk
lab head
Bethany Geary
contact affiliation	University of Manchester
contact email	bethany.geary@manchester.ac.uk
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/2019/10/PXD014708

PRIDE project URI

• PRIDE
  1. PXD014708
     1. Label: PRIDE project
     2. Name: Proteomic analysis of an induced pluripotent stem cell model reveals strategies to treat Juvenile Myelomonocytic Leukaemia