PXD066618 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | LIN28A-Dependent Kinome and Phosphoproteome Reprogramming Promotes Imatinib Resistance |
| Description | Chronic myeloid leukemia (CML) resistance to BCR-ABL tyrosine kinase inhibitors (TKIs) can arise from ABL kinase domain mutations, BCR-ABL fusion gene amplification, or kinase-independent mechanisms. To investigate imatinib-resistance, we performed quantitative mass spectrometry comparing the proteome and phosphoproteome of K562 cells (a standard CML model) and ImR cells, an imatinib-resistant K562 derivative that also exhibits cross-resistance to second- and third-generation BCR-ABL TKIs. In addition to revealing global proteome and phosphoproteome changes associated with drug resistance, we identified LIN28A—a multi-functional RNA-binding protein—as a critical mediator of imatinib resistance. LIN28A was significantly overexpressed and hyperphosphorylated in ImR cells. Depleting LIN28A via shRNA restored imatinib sensitivity, while its ectopic expression in parental K562 cells induced imatinib resistance. Mechanistically, LIN28A coordinates an extensive kinase-substrate network regulating proliferation, survival, and metabolism to drive resistance. Notably, pharmacological inhibition of LIN28A-dependent kinases (PKC, AKT, SGK1, and RPS6K) suppressed ImR proliferation. Midostaurin, a clinical PKC/FLT3 inhibitor used in FLT3-ITD—positive AML, potently re-sensitized ImR cells to imatinib. Our findings suggest that targeting LIN28A and its downstream effectors, particularly PKC, could overcome resistance to imatinib and next-generation BCR-ABL inhibitors. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-01-23 |
| AnnouncementXML | Submission_2026-01-22_18:00:28.807.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Tomonori Kaneko |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | phosphorylated residue |
| Instrument | Q Exactive Plus |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-07-27 07:20:42 | ID requested | |
| ⏵ 1 | 2026-01-22 18:00:29 | announced | |
Publication List
| Hovey OFJ, Frederick MI, Quach QM, Kakadia JH, Wu A, Yang K, Wu T, Ruan X, Kaneko T, Voss C, Heinemann IU, Li SSC, LIN28A-Dependent Kinome and Phosphoproteome Reprogramming Promotes Imatinib Resistance. Mol Cell Proteomics, ():101514(2026) [pubmed] |
| 10.1016/j.mcpro.2026.101514; |
Keyword List
| submitter keyword: Imatinib, K562,TKI resistance, LIN28A, phosphoproteomics |
Contact List
| Shawn SC Li |
|---|
| contact affiliation | Department of Biochemistry, Western University |
| contact email | sli@uwo.ca |
| lab head | |
| Tomonori Kaneko |
|---|
| contact affiliation | Western University |
| contact email | tkaneko@uwo.ca |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD066618
- Label: PRIDE project
- Name: LIN28A-Dependent Kinome and Phosphoproteome Reprogramming Promotes Imatinib Resistance
