التفاصيل البيبلوغرافية
| العنوان: |
Triggering the TCR developmental checkpoint activates a therapeutically targetable tumor suppressive pathway in T-cell leukemia |
| المؤلفون: |
Trinquand, Amelie, dos Santos, Nuno R., Quang, Christine Tran, Rocchetti, Francesca, Zaniboni, Benedetta, Belhocine, Mohamed, de Jesus, Cindy Da Costa, Lhermitte, Ludovic, Tesio, Melania, Dussiot, Michael, Cosset, Francois-Loic, Verhoeyen, Els, Pflumio, Francoise, Ifrah, Norbert, Dombret, Herve, Spicuglia, Salvatore, Chatenoud, Lucienne, Gross, David-Alexandre, Hermine, Olivier, Macintyre, Elizabeth, Ghysdael, Jacques, Asnafi, Vahid |
| المساهمون: |
Sapientia |
| سنة النشر: |
2016 |
| الوصف: |
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 epsilon 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.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. (C) 2016 AACR. |
| نوع الوثيقة: |
journal article |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
2159-8274 |
| DOI: |
10.1158/2159-8290.CD-15-0675 |
| الإتاحة: |
http://hdl.handle.net/10400.1/9312Test |
| حقوق: |
restricted access |
| رقم الانضمام: |
rcaap.com.ualg.sapientia.ualg.pt.10400.1.9312 |
| قاعدة البيانات: |
RCAAP |
