PXD005978

PXD005978 is an original dataset announced via ProteomeXchange.

Title	Signaling network diversification during differentiation sensitizes AML cells to PAK and MEK inhibitors
Description	A main requirement for precision medicine is the identification of patients that are more likely to respond to a particular drug. AML is a heterogeneous disease in which molecules associated to kinase signaling are frequently mutated. However, no kinase inhibitor has been approved for the treatment of this malignancy. Thus, patient stratification requires new molecular profiling techniques in addition of to the current sequencing strategies. We have used a multiomics approach that combines proteomics, phosphoproteomics, mass cytometry and DNA sequencing to classify primary AML cells derived from 36 patients. Comprehensive integrative analysis identified molecular signatures based on phosphopeptide abundance or surface marker expression that separate AML cases according to their differentiation status. Differentiated cells presented a particular pattern of protein phosphorylation, an enrichment in the activity of several kinases and a higher sensitivity to PAK, MEK and PKC/FLT3 inhibitors. In addition, mutations in proteins closely linked to kinase signaling were more frequent on differentiated cells. Interestingly the set of patients with differentiated cells as clustered by marker expression signatures showed an increased overall survival in our set of patients and in the TCGA database registered cohort. Thus, molecular differentiation signatures could be used as prognosis and drug response markers in order to implement the application of precision medicine in AML patients.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:02:10.443.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD005978
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Pedro Casado-Izquierdo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; deaminated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-02-27 05:04:00	ID requested
1	2020-04-14 23:46:42	announced
⏵ 2	2024-10-22 05:02:18	announced	2024-10-22: Updated project metadata.

Casado P, Wilkes EH, Miraki-Moud F, Hadi MM, Rio-Machin A, Rajeeve V, Pike R, Iqbal S, Marfa S, Lea N, Best S, Gribben J, Fitzgibbon J, Cutillas PR, Proteomic and genomic integration identifies kinase and differentiation determinants of kinase inhibitor sensitivity in leukemia cells. Leukemia, 32(8):1818-1822(2018) [pubmed]

10.6019/PXD005978;

10.1038/s41375-018-0032-1;

curator keyword: Biomedical

submitter keyword: AML, Phosphoproteomics, Kinase-Signalling, Kinase-Inhibitors

Pedro R. Cutillas
contact affiliation	Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London
contact email	p.cutillas@qmul.ac.uk
lab head
Pedro Casado-Izquierdo
contact affiliation	Cell Signalling
contact email	p.m.casado-izquierdo@qmul.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD005978
     1. Label: PRIDE project
     2. Name: Signaling network diversification during differentiation sensitizes AML cells to PAK and MEK inhibitors