PXD073522 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | FBXO3-mediated DUSP9 ubiquitination promotes leukemia stem cell maintenance and tyrosine kinase inhibitor resistance in chronic myeloid leukemia |
| Description | Eradicating 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. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-01-25 |
| AnnouncementXML | Submission_2026-01-25_14:54:06.935.xml |
| DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD073522 |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Xudong Li |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Q Exactive HF |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
| 0 | 2026-01-25 13:59:09 | ID requested | |
| ⏵ 1 | 2026-01-25 14:54:07 | announced | |
Publication List
Keyword List
| submitter keyword: TKIs resistance, FBXO3, CML-LSCs, DUSP9,Chronic myeloid leukemia |
Contact List
| Xudong Li |
| contact affiliation | Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China |
| contact email | 19937887913@163.com |
| lab head | |
| Xudong Li |
| contact affiliation | henan cancer hospital |
| contact email | 19937887913@163.com |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD073522
- Label: PRIDE project
- Name: FBXO3-mediated DUSP9 ubiquitination promotes leukemia stem cell maintenance and tyrosine kinase inhibitor resistance in chronic myeloid leukemia