{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T04:44:10Z","timestamp":1775191450435,"version":"3.50.1"},"reference-count":50,"publisher":"American Association for Cancer Research (AACR)","issue":"9","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cancer onset and progression involves the accumulation of multiple oncogenic hits, which are thought to dominate or bypass the physiologic regulatory mechanisms in tissue development and homeostasis. We demonstrate in T-cell acute lymphoblastic leukemia (T-ALL) that, irrespective of the complex oncogenic abnormalities underlying tumor progression, experimentally induced, persistent T-cell receptor (TCR) signaling has antileukemic properties and enforces a molecular program resembling thymic negative selection, a major developmental event in normal T-cell development. Using mouse models of T-ALL, we show that induction of TCR signaling by high-affinity self-peptide\/MHC or treatment with monoclonal antibodies to the CD3\u03f5 chain (anti-CD3) causes massive leukemic cell death. Importantly, anti-CD3 treatment hampered leukemogenesis in mice transplanted with either mouse- or patient-derived T-ALLs. These data provide a strong rationale for targeted therapy based on anti-CD3 treatment of patients with TCR-expressing T-ALL and demonstrate that endogenous developmental checkpoint pathways are amenable to therapeutic intervention in cancer cells.<\/jats:p>\n                  <jats:p>Significance: T-ALLs are aggressive malignant lymphoid proliferations of T-cell precursors characterized by high relapse rates and poor prognosis, calling for the search for novel therapeutic options. Here, we report that the lineage-specific TCR\/CD3 developmental checkpoint controlling cell death in normal T-cell progenitors remains switchable to induce massive tumor cell apoptosis in T-ALL and is amenable to preclinical therapeutic intervention. Cancer Discov; 6(9); 972\u201385. \u00a92016 AACR.<\/jats:p>\n                  <jats:p>See related commentary by Lemonnier and Mak, p. 946.<\/jats:p>\n                  <jats:p>This article is highlighted in the In This Issue feature, p. 932<\/jats:p>","DOI":"10.1158\/2159-8290.cd-15-0675","type":"journal-article","created":{"date-parts":[[2016,6,29]],"date-time":"2016-06-29T00:13:16Z","timestamp":1467159196000},"page":"972-985","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Triggering the TCR Developmental Checkpoint Activates a Therapeutically Targetable Tumor Suppressive Pathway in T-cell Leukemia"],"prefix":"10.1158","volume":"6","author":[{"given":"Am\u00e9lie","family":"Trinquand","sequence":"first","affiliation":[{"name":"1Universit\u00e9 Paris Descartes Sorbonne Cit\u00e9, Institut Necker-Enfants Malades (INEM), Institut national de recherche m\u00e9dicale (INSERM) U1151, and Laboratory of Onco-Hematology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), H\u00f4pital Necker Enfants-Malades, Paris, France."}]},{"given":"Nuno R.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"2Centre for Biomedical Research (CBMR), University of Algarve, Faro, Portugal."},{"name":"3Institut Curie, PSL Research University, CNRS UMR 3348, Orsay, France."}]},{"given":"Christine","family":"Tran Quang","sequence":"additional","affiliation":[{"name":"3Institut Curie, PSL Research University, CNRS UMR 3348, Orsay, France."},{"name":"4Universit\u00e9 Paris Sud, Universit\u00e9 Paris-Saclay, CNRS UMR 3348, Orsay, France."}]},{"given":"Francesca","family":"Rocchetti","sequence":"additional","affiliation":[{"name":"3Institut Curie, PSL Research University, CNRS UMR 3348, Orsay, France."},{"name":"4Universit\u00e9 Paris Sud, Universit\u00e9 Paris-Saclay, CNRS UMR 3348, Orsay, France."}]},{"given":"Benedetta","family":"Zaniboni","sequence":"additional","affiliation":[{"name":"3Institut Curie, PSL Research University, CNRS UMR 3348, Orsay, France."},{"name":"4Universit\u00e9 Paris Sud, Universit\u00e9 Paris-Saclay, CNRS UMR 3348, Orsay, France."}]},{"given":"Mohamed","family":"Belhocine","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 Paris Descartes Sorbonne Cit\u00e9, Institut Necker-Enfants Malades (INEM), Institut national de recherche m\u00e9dicale (INSERM) U1151, and Laboratory of Onco-Hematology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), H\u00f4pital Necker Enfants-Malades, Paris, France."},{"name":"5Technological Advances for Genomics and Clinics (TAGC), INSERM U1090, Universit\u00e9 de la M\u00e9diterran\u00e9e, Marseille, France."}]},{"given":"Cindy","family":"Da Costa de Jesus","sequence":"additional","affiliation":[{"name":"3Institut Curie, PSL Research University, CNRS UMR 3348, Orsay, France."},{"name":"4Universit\u00e9 Paris Sud, Universit\u00e9 Paris-Saclay, CNRS UMR 3348, Orsay, France."}]},{"given":"Ludovic","family":"Lhermitte","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 Paris Descartes Sorbonne Cit\u00e9, Institut Necker-Enfants Malades (INEM), Institut national de recherche m\u00e9dicale (INSERM) U1151, and Laboratory of Onco-Hematology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), H\u00f4pital Necker Enfants-Malades, Paris, France."}]},{"given":"Melania","family":"Tesio","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 Paris Descartes Sorbonne Cit\u00e9, Institut Necker-Enfants Malades (INEM), Institut national de recherche m\u00e9dicale (INSERM) U1151, and Laboratory of Onco-Hematology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), H\u00f4pital Necker Enfants-Malades, Paris, France."}]},{"given":"Michael","family":"Dussiot","sequence":"additional","affiliation":[{"name":"6INSERM UMR 1163 and CNRS ERL 8654, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Laboratory of Excellence GR-Ex, Imagine Institute and Paris Descartes University, Sorbonne Paris Cit\u00e9, Paris, France."}]},{"given":"Fran\u00e7ois-Lo\u00efc","family":"Cosset","sequence":"additional","affiliation":[{"name":"7CIRI, EVIR Team, INSERM U1111, CNRS UMR 5308, Universit\u00e9 de Lyon-1, ENS de Lyon, Lyon, France."}]},{"given":"Els","family":"Verhoeyen","sequence":"additional","affiliation":[{"name":"7CIRI, EVIR Team, INSERM U1111, CNRS UMR 5308, Universit\u00e9 de Lyon-1, ENS de Lyon, Lyon, France."},{"name":"8INSERM U1065, C3M, Equipe \u201cContr\u00f4le M\u00e9tabolique des Morts Cellulaires,\u201d Nice, France."}]},{"given":"Fran\u00e7oise","family":"Pflumio","sequence":"additional","affiliation":[{"name":"9Laboratoire des Cellules Souches H\u00e9matopo\u00ef\u00e9tiques et Leuc\u00e9miques, UMR 967, INSERM, Commissariat \u00e0 l'Energie Atomique, Universit\u00e9 Paris Diderot, Universit\u00e9 Paris 11, Institut de Radiobiologie Cellulaire et Mol\u00e9culaire, \u00e9quipe labellis\u00e9e Ligue Nationale contre le Cancer, Fontenay-aux-Roses, France."}]},{"given":"Norbert","family":"Ifrah","sequence":"additional","affiliation":[{"name":"10PRES LUNAM, CHU Angers service des Maladies du Sang et INSERM U892, Angers, France."}]},{"given":"Herv\u00e9","family":"Dombret","sequence":"additional","affiliation":[{"name":"11Universit\u00e9 Paris 7, H\u00f4pital Saint-Louis, AP-HP, Department of Hematology and Institut Universitaire d'H\u00e9matologie, Paris, France."}]},{"given":"Salvatore","family":"Spicuglia","sequence":"additional","affiliation":[{"name":"5Technological Advances for Genomics and Clinics (TAGC), INSERM U1090, Universit\u00e9 de la M\u00e9diterran\u00e9e, Marseille, France."}]},{"given":"Lucienne","family":"Chatenoud","sequence":"additional","affiliation":[{"name":"12Institut Necker Enfants Malades, INSERM U1151, CNRS UMR 8253, 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France."}]},{"given":"Elizabeth","family":"Macintyre","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 Paris Descartes Sorbonne Cit\u00e9, Institut Necker-Enfants Malades (INEM), Institut national de recherche m\u00e9dicale (INSERM) U1151, and Laboratory of Onco-Hematology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), H\u00f4pital Necker Enfants-Malades, Paris, France."}]},{"given":"Jacques","family":"Ghysdael","sequence":"additional","affiliation":[{"name":"3Institut Curie, PSL Research University, CNRS UMR 3348, Orsay, France."},{"name":"4Universit\u00e9 Paris Sud, Universit\u00e9 Paris-Saclay, CNRS UMR 3348, Orsay, France."}]},{"given":"Vahid","family":"Asnafi","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 Paris Descartes Sorbonne Cit\u00e9, Institut Necker-Enfants Malades (INEM), Institut national de recherche m\u00e9dicale (INSERM) U1151, and Laboratory of Onco-Hematology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), H\u00f4pital 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