Evidence map›Paper›PMID 41565205›Full record

ArticleMolecular & cellular proteomics : MCP2026

LIN28A-Dependent Kinome and Phosphoproteome Reprogramming Promotes Imatinib Resistance.

Owen F J Hovey, Mallory I Frederick, Quan M Quach, Jenica H Kakadia, Alyssa Wu, Kyle Yang, Tingting Wu, Xiang Ruan, Tomonori Kaneko, Courtney Voss and 2 more

Abstract read
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In one paragraph

Article in Molecular & cellular proteomics : MCP, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Owen F J HoveyDepartment of Biochemistry, Western University, London, Ontario, Canada.
Mallory I FrederickDepartment of Biochemistry, Western University, London, Ontario, Canada.
Quan M QuachDepartment of Biochemistry, Western University, London, Ontario, Canada.
Jenica H KakadiaDepartment of Biochemistry, Western University, London, Ontario, Canada.
Alyssa WuDepartment of Biochemistry, Western University, London, Ontario, Canada.
Kyle YangDepartment of Biochemistry, Western University, London, Ontario, Canada.
Tingting WuDepartment of Biochemistry, Western University, London, Ontario, Canada.
Xiang RuanDepartment of Biochemistry, Western University, London, Ontario, Canada.
Tomonori KanekoDepartment of Biochemistry, Western University, London, Ontario, Canada.
Courtney VossDepartment of Biochemistry, Western University, London, Ontario, Canada.
Ilka U HeinemannDepartment of Biochemistry, Western University, London, Ontario, Canada. Electronic address: ilka.heinemann@uwo.ca.
Shawn S C LiDepartment of Biochemistry, Western University, London, Ontario, Canada; Department of Oncology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. Electronic address: sli@uwo.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic myeloid leukemia (CML) resistance to BCR-ABL tyrosine kinase inhibitors 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 tyrosine kinase inhibitors. In addition to revealing global proteome and phosphoproteome changes associated with drug resistance, we identified LIN28A-a multifunctional 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 resensitized 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.

Indexed as

Drug Resistance, NeoplasmImatinib MesylatePhosphoproteinsProteomeRNA-Binding ProteinsAntineoplastic AgentsCell Line, TumorCell ProliferationFusion Proteins, bcr-ablHumansK562 CellsLeukemia, Myelogenous, Chronic, BCR-ABL PositivePhosphorylationProtein Kinase InhibitorsTyrosine Kinase InhibitorsAntineoplastic AgentsFusion Proteins, bcr-ablImatinib MesylateLin28A protein, humanPhosphoproteinsProtein Kinase InhibitorsProteomeRNA-Binding ProteinsTyrosine Kinase InhibitorsAKT/mTOR signallingchronic myeloid leukemiaimatinib resistancekinome reprogramingLIN28A

Identifiers

PMID41565205
PMCPMC13091335

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.