PXD024807

PXD024807 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomic Profiling of T-Cell Acute Lymphoblastic Leukemia Identifies Targetable Kinases and Combination Treatments
Description	Protein kinase inhibitors are amongst the most successful cancer treatments, but targetable kinases activated by gene fusions are rare in T-ALL (e.g., NUP214-ABL1). Nevertheless, leukemic blasts rely on enhanced kinase signaling to sustain dysregulated proliferation. Protein kinases can be hyper-activated in the absence of defects in their genes. Thus, phospho-proteomics can provide information on pathway activation, signaling networks and aberrant kinases activities that offer important opportunities for targeted therapies. Here, we performed mass spectrometry-based global profiling of tyrosine, serine, and threonine phosphorylation in a panel of 11 T-ALL cell lines to identify potential targetable kinases. We report a comprehensive dataset consisting of 21,000 phosphosites on 4896 phosphoproteins, including 217 kinases. We identify several Src-family members (LCK, SRC, FYN, YES1) as well as the cyclin-dependent kinases CDK1 and CDK2 as broadly activated in our panel. We validate highly active kinases as putative target for therapy in vitro and propose potential novel combination treatment strategies, such as the inhibition of the insulin-like growth factor receptor (IGF-1R) signaling pathway to increase the sensitivity to dasatinib treatment in T-ALL.
HostingRepository	PRIDE
AnnounceDate	2022-02-21
AnnouncementXML	Submission_2022-02-21_03:17:51.041.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sander Piersma
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-17 11:19:34	ID requested
⏵ 1	2022-02-21 03:17:51	announced

Dataset with its publication pending

submitter keyword: Human, T-ALL, T-Cell Acute Lymphoblastic Leukemia, label-free, single-shot, pTyr, phosphoproteomics

Connie Jimenez
contact affiliation	Amsterdam UMC, Vrije Universiteit Amsterdam, Medical Oncology, Cancer Center Amsterdam, OncoProteomics Laboratory, Amsterdam, Netherlands
contact email	c.jimenez@amsterdamumc.nl
lab head
Sander Piersma
contact affiliation	Amsterdam UMC
contact email	s.piersma@amsterdamumc.nl
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/2022/02/PXD024807

PRIDE project URI

• PRIDE
  1. PXD024807
     1. Label: PRIDE project
     2. Name: Phosphoproteomic Profiling of T-Cell Acute Lymphoblastic Leukemia Identifies Targetable Kinases and Combination Treatments