PXD007237

PXD007237 is an original dataset announced via ProteomeXchange.

Title	The phosphoproteomic landscape of 16 Acute Myeloid Leukemia (AML) cell lines
Description	Acute myeloid leukemia (AML) is a clonal hematopoietic malignancy, characterized by expansion of immature leukemic blasts in the bone marrow. In AML, specific tyrosine kinases have been implicated in leukemogenesis, and are associated with poor treatment outcome. However, targeted therapy using kinase inhibitors (KIs) has had limited success, and may be improved by proper patient selection. We performed phosphotyrosine (pY) based, label-free phosphoproteomics to identify hyperphosphorylated, active kinases in AML cell lines as targets and predictive biomarkers to select KIs for treatment. We identified 3605 class I phosphorylation sites in 16 AML cell lines (EOL-1, KG-1a, MM6, KG-1, ME-1, NB-4, Kasumi-3, MV4-11, THP-1, HEL, HL-60, Kasumi-1, Kasumi-6, ML-2, OCI-AML3, MOLM-13) that exhibited large variation in the number and level of phosphopeptides per cell line (241-2764). Ranking analyses successfully pinpointed the hyperactive kinases PDGFRA, FGFR1, KIT, and FLT3 in eight cell lines with a corresponding kinase mutation. Additionally, we identified unexpected drivers in two more cell lines (PDGFRA in Kasumi-3 and FLT3 in MM6) which proved sensitive to specific kinase inhibitors. Six cell lines without a clear receptor tyrosine kinase (RTK) driver showed evidence of MAPK1/3 activation, consistent with the presence of activating RAS mutations. Our data show the potential of pY phosphoproteomics to identify key drivers in AML cells, and the predictive value of the phosphoproteome profiles in TKi selection for targeted treatment.
HostingRepository	PRIDE
AnnounceDate	2019-11-11
AnnouncementXML	Submission_2020-03-24_00:43:53.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; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-08-09 06:07:49	ID requested
1	2018-10-23 15:53:19	announced
⏵ 2	2020-03-24 00:43:55	announced	2020-03-24: Updated publication reference for PubMed record(s): 32102969, 28928222.

Jinnelov A, Ali L, Tinti M, G, ü, ther MLS, Ferguson MAJ, display different and predictable peptide acceptor specificities. J Biol Chem, 292(49):20328-20341(2017) [pubmed]

van Alphen C, Cloos J, Beekhof R, Cucchi DGJ, Piersma SR, Knol JC, Henneman AA, Pham TV, van Meerloo J, Ossenkoppele GJ, Verheul HMW, Janssen JJWM, Jimenez CR, Phosphotyrosine-based Phosphoproteomics for Target Identification and Drug Response Prediction in AML Cell Lines. Mol Cell Proteomics, 19(5):884-899(2020) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Human, Tyrosine kinase, Acute Myeloid Leukemia, AML, phosphokinase ranking, label-free, single-shot, phosphoproteomics

Connie Ramona Jimenez
contact affiliation	OncoProteomics Laboratory, Dept of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
contact email	c.jimenez@vumc.nl
lab head
Sander Piersma
contact affiliation	OncoProteomics Laboratory, dept of Medical Oncology, VUmc Medical Center, Amsterdam, The Netherlands
contact email	s.piersma@vumc.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/2019/11/PXD007237

PRIDE project URI

• PRIDE
  1. PXD007237
     1. Label: PRIDE project
     2. Name: The phosphoproteomic landscape of 16 Acute Myeloid Leukemia (AML) cell lines