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PXD073522

PXD073522 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleFBXO3-mediated DUSP9 ubiquitination promotes leukemia stem cell maintenance and tyrosine kinase inhibitor resistance in chronic myeloid leukemia
DescriptionEradicating leukemic stem cells (LSCs) and overcoming tyrosine kinase inhibitor (TKI) resistance is urgent for chronic myeloid leukemia (CML) treatment. We find that F-box protein 3 (FBXO3) is highly upregulated in CD34+ CML stem cells from TKI-resistant patients and identify it as an innovative CML-LSC marker via single-cell RNA sequencing (scRNA-seq). FBXO3 deficiency induces apoptosis and reduces proliferation of CML cell lines and LSCs in vitro and in vivo, with minimal effects on normal CD34+ hematopoietic stem cells (HSCs). Mechanistically, FBXO3 interacts with DUSP9 to promote its ubiquitination and activate the MAPK pathway, critical for CML cell activity. DUSP9 knockdown partially reverses FBXO3 deficiency-mediated LSC elimination. Furthermore, FBXO3 inhibitor monotherapy or combination with imatinib effectively eradicates CML-LSCs, overcomes TKI resistance, and spares normal hematopoiesis. Collectively, our findings highlight FBXO3’s role in CML progression and support combining FBXO3 inhibitors with TKIs for durable LSC elimination.
HostingRepositoryPRIDE
AnnounceDate2026-01-25
AnnouncementXMLSubmission_2026-01-25_14:54:06.935.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD073522
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterXudong Li
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-01-25 13:59:09ID requested
12026-01-25 14:54:07announced
Publication List
10.6019/PXD073522;
Keyword List
submitter keyword: TKIs resistance, FBXO3, CML-LSCs, DUSP9,Chronic myeloid leukemia
Contact List
Xudong Li
contact affiliationDepartment of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
contact email19937887913@163.com
lab head
Xudong Li
contact affiliationhenan cancer hospital
contact email19937887913@163.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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