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PXD005734

PXD005734 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleABPP of Ibrutinib Resistance in B Cell Malignancies
DescriptionIbrutinib,a novel Bruton'styrosine kinase inhibitor, demonstrated high response rates in B-cell lymphomas but a growing number of ibrutinib treated patients relapse with resistance, fulminant progression and accelerated mortality. Using chemical proteomics and a high-throughput ex vivo assay in a reconstructed tumor microenvironment (TME), we determined the molecular basis for ibrutinib activity and mechanism of acquired ibrutinib resistance. Reciprocal activation of PI3K-AKT-mTOR and integrin β1 signaling were identified as a signaling hub of kinome for ibrutinib resistance, resulting in enforced TME-lymphoma interactions, promoting mantle cell lymphoma (MCL) growth and drug resistance. Combinatorial disruption of BCR signaling and ibrutinib resistance associated pathways led to release of MCL cells from TME, reversal of drugresistance and enhanced anti-MCL activity in murine and patient-derived xenograft models. This study integrated TME-mediated de-novo and acquired drug resistance mechanisms and provides the rationale for novel combination therapeutic strategy against MCL and other B cell malignancies.
HostingRepositoryPRIDE
AnnounceDate2018-10-26
AnnouncementXMLSubmission_2018-10-26_10:27:07.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD005734
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterJohn Koomen
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListOxidation; Biotin:Thermo-88310; Carbamidomethyl
InstrumentLTQ Orbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02017-01-17 05:35:29ID requested
12018-10-26 10:27:08announced
Publication List
Zhao X, Lwin T, Silva A, Shah B, Tao J, Fang B, Zhang L, Fu K, Bi C, Li J, Jiang H, Meads MB, Jacobson T, Silva M, Distler A, Darville L, Zhang L, Han Y, Rebatchouk D, Di Liberto M, Moscinski LC, Koomen JM, Dalton WS, Shain KH, Wang M, Sotomayor E, Tao J, Unification of de novo and acquired ibrutinib resistance in mantle cell lymphoma. Nat Commun, 8():14920(2017) [pubmed]
Keyword List
curator keyword: Biomedical
submitter keyword: activity-based protein profiling, LC-MS/MS, B-cell cancers, Ibrutinib
Contact List
Jianguo Tao, MD/PhD
contact affiliationMoffitt Cancer Center Tampa, FL, USA
contact emailjianguo.tao@moffitt.org
lab head
John Koomen
contact affiliationMoffitt Cancer Center
contact emailjohn.koomen@moffitt.org
dataset submitter
Full Dataset Link List
Dataset FTP location
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