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PXD024807

PXD024807 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePhosphoproteomic Profiling of T-Cell Acute Lymphoblastic Leukemia Identifies Targetable Kinases and Combination Treatments
DescriptionProtein 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.
HostingRepositoryPRIDE
AnnounceDate2022-02-21
AnnouncementXMLSubmission_2022-02-21_03:17:51.041.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSander Piersma
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-03-17 11:19:34ID requested
12022-02-21 03:17:51announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Human, T-ALL, T-Cell Acute Lymphoblastic Leukemia, label-free, single-shot, pTyr, phosphoproteomics
Contact List
Connie Jimenez
contact affiliationAmsterdam UMC, Vrije Universiteit Amsterdam, Medical Oncology, Cancer Center Amsterdam, OncoProteomics Laboratory, Amsterdam, Netherlands
contact emailc.jimenez@amsterdamumc.nl
lab head
Sander Piersma
contact affiliationAmsterdam UMC
contact emails.piersma@amsterdamumc.nl
dataset submitter
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Dataset FTP location
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