Proteomics

Dataset Information

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The phosphoproteomic landscape of 16 Acute Myeloid Leukemia (AML) cell lines


ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood

DISEASE(S): Acute Leukemia

SUBMITTER: Sander Piersma  

LAB HEAD: Connie Ramona Jimenez

PROVIDER: PXD007237 | Pride | 2019-11-11

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
MaxQuant_Lysate_protein.zip Other
MaxQuant_phospho.zip Other
QE1_140612_OPL1013_CVA_LYSATE_AML_A.raw Raw
QE1_140612_OPL1013_CVA_LYSATE_AML_B.raw Raw
QE1_140612_OPL1013_CVA_LYSATE_AML_C.raw Raw
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Publications

Single-subunit oligosaccharyltransferases of <i>Trypanosoma brucei</i> display different and predictable peptide acceptor specificities.

Jinnelov Anders A   Ali Liaqat L   Tinti Michele M   Güther Maria Lucia S MLS   Ferguson Michael A J MAJ  

The Journal of biological chemistry 20170919 49


<i>Trypanosoma brucei</i> causes African trypanosomiasis and contains three full-length oligosaccharyltransferase (OST) genes; two of which, <i>Tb</i>STT3A and <i>Tb</i>STT3B, are expressed in the bloodstream form of the parasite. These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic <i>N</i>-glycosylation pathways, raising questions as to the basic architecture an  ...[more]

Publication: 1/2

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