Tumor necrosis factor alpha induces senescence and chromosomal instability in human leukemic cells

ABSTRACT Previous studies have documented that Tumor necrosis factor alpha (TNF_α_) is a potent negative regulator of normal hematopoiesis. However, the mechanism by which TNF_α_ acts at the

cellular level is not totally understood. Although apoptotic cell killing appears to be the most common cellular effect of TNF_α_, other studies suggest that this cytokine may elicit other

cellular responses such as prolonged growth inhibition. In this context, we have investigated whether TNF_α_ may induce senescence in hematopoietic cells, which display intrinsic defect in

the apoptotic machinery. The present study described that, in the leukemic KG1 cells, TNF_α_ induced no apoptosis but a senescence state characterized by prolonged growth arrest, increased

_β_-galactosidase activity, p21WAF-1 induction, decreased telomerase activity, telomeric disturbances (shortening, losses, fusions), and additional chromosomal aberrations. Telomerase

inhibition correlated with reduced levels of hTERT transcripts. GM-CSF prevented TNF_α_ effects and allowed leukemic cells to recover growth capacity. Finally, our study shows for the first

time that, at least in some hematopoietic cells, TNF_α_ may induce senescence with important functional consequences, including sustained growth inhibition and genetic instability, and that

this cellular response is efficiently regulated by hematopoietic growth factors. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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T-CELL-MEDIATED TUMOR CONTROL Article Open access 31 March 2025 ONCOGENE-INDUCED SENESCENCE IN HEMATOPOIETIC PROGENITORS FEATURES MYELOID RESTRICTED HEMATOPOIESIS, CHRONIC INFLAMMATION AND

HISTIOCYTOSIS Article Open access 27 July 2021 DYNAMIC BIOLOGICAL CHARACTERISTICS OF HUMAN BONE MARROW HEMATOPOIETIC STEM CELL SENESCENCE Article Open access 12 October 2022 REFERENCES *

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3723–3728. Download references ACKNOWLEDGEMENTS This work was supported by grants from the INSERM, the Fondation de France, and the Association pour la Recherche contre le Cancer. AUTHOR

INFORMATION AUTHORS AND AFFILIATIONS * Institut National de la Santé et de la Recherche Médicale (INSERM) U563, Centre de Physiopathologie de Toulouse Purpan, Place du Docteur Baylac,

Toulouse, 31059, France Odile Beyne-Rauzy, Christian Recher, Nicole Dastugue, Cécile Demur, Guy Laurent & Véronique Mansat-De Mas * Service d'Hématologie, Centre Hospitalier

Universitaire Purpan, Place du Docteur Baylac, Toulouse, 31059, France Christian Recher & Guy Laurent * Laboratoire d'Hématologie, Centre Hospitalier Universitaire Purpan, Place du

Docteur Baylac, Toulouse, 31059, France Nicole Dastugue, Cécile Demur & Véronique Mansat-De Mas * CEA-DSV/DRR/LRO, 18 Route du Panorama, 92265 Fontenay aux roses cedex, France Géraldine

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publications You can also search for this author inPubMed Google Scholar * Géraldine Pottier View author publications You can also search for this author inPubMed Google Scholar * Guy

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AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Beyne-Rauzy, O., Recher, C., Dastugue, N. _et al._ Tumor necrosis factor alpha induces senescence and

chromosomal instability in human leukemic cells. _Oncogene_ 23, 7507–7516 (2004). https://doi.org/10.1038/sj.onc.1208024 Download citation * Received: 19 January 2004 * Revised: 24 June 2004

* Accepted: 29 June 2004 * Published: 23 August 2004 * Issue Date: 30 September 2004 * DOI: https://doi.org/10.1038/sj.onc.1208024 SHARE THIS ARTICLE Anyone you share the following link

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content-sharing initiative KEYWORDS * TNF_α_ * senescence * AML cells * genetic instability