
Tumor necrosis factor alpha induces senescence and chromosomal instability in human leukemic cells
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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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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS SENESCENCE-ASSOCIATED LINEAGE-ABERRANT PLASTICITY EVOKES
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 *
Akiyama M, Hideshima T, Hayashi T, Tai YT, Mitsiades CS, Mitsiades N, Chauhan D, Richardson P, Munshi NC and Anderson KC . (2002). _Cancer Res._, 62, 3876–3882. * Baloch Z, Cohen S and
Coffman FD . (1990). _J. Immunol._, 145, 2908–2913. * Bettaieb A, Record M, Come MG, Bras AC, Chap H, Laurent G and Jaffrezou JP . (1996). _Blood_, 88, 1465–1472. * Bryder D, Ramsfjell V,
Dybedal I, Theilgaard-Monch K, Hogerkorp CM, Adolfsson J, Borge OJ and Jacobsen SE . (2001). _J. Exp. Med._, 194, 941–952. * De Maria R, Zeuner A, Eramo A, Domenichelli C, Bonci D, Grignani
F, Srinivasula SM, Alnemri ES, Testa U and Peschle C . (1999). _Nature_, 401, 489–493. * Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I,
Pereira-Smith O, Peacocke M and Campisi J . (1995). _Proc. Natl. Acad. Sci. USA_, 92, 9363–9367. * Dumont P, Balbeur L, Remacle J and Toussaint O . (2000). _J. Anat._, 197, 529–537. *
Dybedal I, Bryder D, Fossum A, Rusten LS and Jacobsen SE . (2001). _Blood_, 98, 1782–1791. * Gorbunova V, Seluanov A and Pereira-Smith OM . (2002). _J. Biol. Chem._, 277, 38540–38549 (Epub
2002 July 24). * Jaffrezou JP, Levade T, Bettaieb A, Andrieu N, Bezombes C, Maestre N, Vermeersch S, Rousse A and Laurent G . (1996). _EMBO J._, 15, 2417–2424. * Jeoung DI, Tang B and
Sonenberg M . (1995). _J. Biol. Chem._, 270, 18367–18373. * Kelly ML, Tang Y, Rosensweig N, Clejan S and Beckman BS . (1998). _Blood_, 92, 416–424. * Kitagawa M, Saito I, Kuwata T, Yoshida
S, Yamaguchi S, Takahashi M, Tanizawa T, Kamiyama R and Hirokawa K . (1997). _Leukemia_, 11, 2049–2054. * Maser RS and DePinho RA . (2002). _Science_, 297, 565–569. * Mathieu N, Pirzio L,
Freulet-Marriere MA, Desmaze C and Sabatier L . (2004). _Cell Mol. Life Sci._, 61, 641–656. * Murase T, Hotta T, Saito H and Ohno R . (1987). _Blood_, 69, 467–472. * Nathan I, Dizdaroglu M,
Bernstein L, Junker U, Lee C, Muegge K and Durum SK . (2000). _Cytokine_, 12, 881–887. * Ogretmen B, Kraveka JM, Schady D, Usta J, Hannun YA, Obeid LM, Wood R, Luberto C and Birbes H .
(2001a). _J. Biol. Chem._, 276, 32506–32514. * Ogretmen B, Schady D, Usta J, Wood R, Kraveka JM, Luberto C, Birbes H, Hannun YA and Obeid LM . (2001b). _J. Biol. Chem._, 276, 24901–24910. *
Oster W, Cicco NA, Klein H, Hirano T, Kishimoto T, Lindemann A, Mertelsmann RH and Herrmann F . (1989). _J. Clin. Invest._, 84, 451–457. * O'Sullivan JN, Bronner MP, Brentnall TA,
Finley JC, Shen WT, Emerson S, Emond MJ, Gollahon KA, Moskovitz AH, Crispin DA, Potter JD and Rabinovitch PS . (2002). _Nat. Genet._, 32, 280–284. * Park YM, Han MY, Blackburn RV and Lee YJ
. (1998). _J. Cell. Physiol._, 174, 27–34. * Quentmeier H, Dirks WG, Fleckenstein D, Zaborski M and Drexler HG . (2000). _Exp. Hematol._, 28, 1008–1015. * Quillet-Mary A, Mansat V, Duchayne
E, Come MG, Allouche M, Bailly JD, Bordier C and Laurent G . (1996). _Leukemia_, 10, 417–425. * Sugimoto K, Toyoshima H, Sakai R, Miyagawa K, Hagiwara K, Ishikawa F, Takaku F, Yazaki Y and
Hirai H . (1992). _Blood_, 79, 2378–2383. * Tobler A, Johnston D and Koeffler HP . (1987). _Blood_, 70, 200–205. * Tsukada Y, Nakamura T, Iimura M, Iizuka BE and Hayashi N . (2002). _Am. J.
Gastroenterol._, 97, 2820–2828. * von Zglinicki T . (2002). _Trends Biochem. Sci._, 27, 339–344. * Yang J, Chang E, Cherry AM, Bangs CD, Oei Y, Bodnar A, Bronstein A, Chiu CP and Herron GS .
(1999). _J. Biol. Chem._, 274, 26141–26148. * Young NS . (2000). _Semin. Hematol._, 37, 3–14. * Zhu J, Wang H, Bishop JM and Blackburn EH . (1999). _Proc. Natl. Acad. Sci. USA_, 96,
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
Pottier & Laure Sabatier Authors * Odile Beyne-Rauzy View author publications You can also search for this author inPubMed Google Scholar * Christian Recher View author publications You
can also search for this author inPubMed Google Scholar * Nicole Dastugue View author publications You can also search for this author inPubMed Google Scholar * Cécile Demur View author
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
Laurent View author publications You can also search for this author inPubMed Google Scholar * Laure Sabatier View author publications You can also search for this author inPubMed Google
Scholar * Véronique Mansat-De Mas View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Véronique Mansat-De Mas. RIGHTS
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