Apoptosis and autophagy have opposite roles on imatinib-induced K562 leukemia cell senescence
Open accessAbstract
Imatinib, the anti-Abl tyrosine kinase inhibitor used as first-line therapy in chronic myeloid leukemia (CML), eliminates CML cells mainly by apoptosis and induces autophagy. Analysis of imatinib-treated K562 cells reveals a cell population with cell cycle arrest, p27 increase and senescence-associated beta galactosidase (SA-β-Gal) staining. Preventing apoptosis by caspase inhibition decreases annexin V-positive cells, caspase-3 cleavage and increases the SA-β-Gal-positive cell population. In addition, a concomitant increase of the cell cycle inhibitors p21 and p27 is detected emphasizing the senescent phenotype. Inhibition of apoptosis by targeting Bim expression or overexpression of Bcl2 potentiates senescence. The inhibition of autophagy by silencing the expression of the proteins ATG7 or Beclin-1 prevents the increase of SA-β-Gal staining in response to imatinib plus Z-Vad. In contrast, in apoptotic-deficient cells (Bim expression or overexpression of Bcl2), the inhibition of autophagy did not significantly modify the SA-β-Gal-positive cell population. Surprisingly, targeting autophagy by inhibiting ATG5 is accompanied by a strong SA-β-Gal staining, suggesting a specific inhibitory role on senescence. These results demonstrate that in addition to apoptosis and autophagy, imatinib induced senescence in K562 CML cells. Moreover, apoptosis is limiting the senescent response to imatinib, whereas autophagy seems to have an opposite role.
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K562 is difficult to become senescent, despite being senescence-inducible by certain therapies such as imatinib.
“K562, the p53-deficient cancer cell line, is difficult to become senescent, despite senescence-inducible by certain therapies, such as imatinib.122,123”
From Single-cell senescence identification reveals senescence heterogeneity, trajectory, and modulators (2024) · cites this paper as [122]
The Results report senescence markers in imatinib-treated K562 cells, and the Discussion describes an imatinib-induced senescence-like change (page not provided). The passages do not establish that K562 cells are generally difficult to make senescent or identify them as p53-deficient. (LLM, conf=0.86)
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- Druker BJ Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells Nat Med 1996 2 561 566 8616716
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- Authors
- Drullion, C., Trégoat, C., Lagarde, V, Tan, S., Gioia, R., Priault, M., Djavaheri-Mergny, M., Brisson, A., Auberger, P., Mahon, F.-X., & Pasquet, J.-M.
- Affiliations
- Université de Bordeaux (FR)
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Pasquet, J-M
- Venue
- Cell Death & Disease
- Published
- 2012-08-16
- Volume
- 3
- Issue
- 8
- Pages
- e373-e373
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC3434662
- OpenAlex
- W2052829673
- Cited by
- 88
- References
- 43
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 8 · 2023: 3 · 2022: 3 · 2021: 7 · 2020: 4 · 2019: 7 · 2018: 8 · 2017: 8 · 2016: 3 · 2015: 5 · 2014: 11 · 2013: 9 · 2012: 1
- FWCI
- 5.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Cell Death and Disease (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Ligue Contre le Cancer
- Novartis Pharma
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- imatinib, K562 cells, chronic myeloid leukemia, cellular senescence, apoptosis, autophagy, senescence-associated β-galactosidase, p27, p21, building information modeling, Bcl-2, ATG5, ATG7, Beclin-1, caspase inhibition, ABL tyrosine kinase inhibitors
- MeSH terms
- Imatinib Mesylate, Beclin-1, Autophagy-Related Protein 7, Bcl-2-Like Protein 11, Antineoplastic Agents, Autophagy, Benzamides, Humans, Membrane Proteins, Oligopeptides, Piperazines, Proto-Oncogene Proteins, Pyrimidines, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Cellular Senescence, Apoptosis, Proto-Oncogene Proteins c-bcl-2, K562 Cells, RNA Interference, RNA, Small Interfering, Ubiquitin-Activating Enzymes, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase Inhibitor p27, Apoptosis Regulatory Proteins, Caspase 3, Cell Cycle Checkpoints
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