{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:49:24Z","timestamp":1790920164222,"version":"4.1.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2008,11,1]],"date-time":"2008-11-01T00:00:00Z","timestamp":1225497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of long-lived monoclonal B cells mostly arrested at the G0\/G1 phase of the cell cycle. CLL cells strongly express intracellular melanoma differentiation-associated gene-7 (MDA7)\/IL-24. However, adenovirus-delivered MDA7 was reported to be cytotoxic in several tumor cell lines. We report herein that rIL-24 alone had no effect; however, sequential incubation with rIL-2 and rIL-24 reduced thymidine incorporation by 50% and induced apoptosis of CLL cells in S and G2\/M phases of the cell cycle, but not of normal adult blood or tonsil B cells. IL-24 stimulated STAT3 phosphorylation in IL-24R1-transfected cells but not in normal or CLL B cells. In contrast, IL-24 reversed the IL-2-induced phosphorylation of STAT3 in CLL, and this effect was neutralized by anti-IL-24 Ab. Phospho- (P)STAT3 inhibition induced by IL-24 was reversed by pervanadate, an inhibitor of tyrosine phosphatases. The addition of rIL-24 to IL-2-activated CLL B cells resulted in increases of transcription, protein synthesis. and phosphorylation of p53. The biological effects of IL-24 were reversed by the p53 inhibitor pifithrin-\u03b1 and partly by the caspase inhibitor zvad. Troglitazone (a protein tyrosine phosphatase, PTP1B activator) phosphatase inhibited PSTAT3 and augmented p53 expression. PSTAT3 is a transcriptional repressor of p53, and therefore IL-24 induction of p53 secondary to PSTAT3 dephosphorylation may be sensed as a stress signal and promote apoptosis in cycling cells. This model explains why IL-24 can protect some resting\/differentiated cells and be deleterious to proliferating cells.<\/jats:p>","DOI":"10.4049\/jimmunol.181.9.6051","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:03:28Z","timestamp":1397862208000},"page":"6051-6060","source":"Crossref","is-referenced-by-count":36,"title":["IL-24 Induces Apoptosis of Chronic Lymphocytic Leukemia B Cells Engaged into the Cell Cycle through Dephosphorylation of STAT3 and Stabilization of p53 Expression"],"prefix":"10.1093","volume":"181","author":[{"given":"Alexander","family":"Sainz-Perez","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U764, IFR 13, Universit\u00e9 Paris XI , Clamart,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Gary-Gouy","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U764, IFR 13, Universit\u00e9 Paris XI , Clamart,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Gaudin","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U764, IFR 13, Universit\u00e9 Paris XI , Clamart,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghyath","family":"Maarof","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U764, IFR 13, Universit\u00e9 Paris XI , Clamart,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Marfaing-Koka","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019H\u00e9matologie, H\u00f4pital Antoine B\u00e9cl\u00e8re , Clamart,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"de Revel","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9matologie, H\u00f4pital d\u2019Instruction des Arm\u00e9es Percy , Clamart,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Dalloul","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U764, IFR 13, Universit\u00e9 Paris XI , Clamart,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,11,1]]},"reference":[{"key":"2025032700362952600_R1","first-page":"223","article-title":"The family of IL-10-related cytokines and their receptors: related but to what extent?","volume-title":"Cytokine Growth Factor Rev.","year":"2002"},{"key":"2025032700362952600_R2","first-page":"667","article-title":"Class II cytokine receptors and their ligands: key antiviral and inflammatory modulators","volume-title":"Nat. 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