Repository logo
 
Publication

Triggering the TCR developmental checkpoin activates a therapeutically targetable tumor suppressive pathway in T-cell leukemia

2016-07Journal article Open access
Simple item page
dc.contributor.authorTrinquand, A.
dc.contributor.authorRodrigues Dos Santos, Nuno
dc.contributor.authorTran Quang, C.
dc.contributor.authorBelhocine, M.
dc.contributor.authorJesus, C. da Costa de
dc.contributor.authorLhermitte, L.
dc.contributor.authorTesio, M.
dc.contributor.authorDussiot, M.
dc.contributor.authorCosset, F. L.
dc.contributor.authorVerhoeyen, E.
dc.contributor.authorPflumio, F.
dc.contributor.authorIfrah, N.
dc.contributor.authorDombret, H.
dc.contributor.authorSpicuglia, S.
dc.contributor.authorChatenoud, L.
dc.contributor.authorGross, David-Alexandre
dc.contributor.authorHermine, Olivier
dc.contributor.authorMacintyre, E.
dc.contributor.authorGhysdael, Jacques
dc.contributor.authorAsnafi, V.
dc.date.accessioned2017-04-07T15:56:32Z
dc.date.available2017-04-07T15:56:32Z
dc.date.issued2016-07
dc.description.abstractCancer 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-affi nity selfpeptide/MHC or treatment with monoclonal antibodies to the CD3ε 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.
dc.identifier.issn0390-6078
dc.identifier.urihttp://hdl.handle.net/10400.1/9448
dc.language.isoeng
dc.peerreviewedyes
dc.publisherEuropean Hematol Assoc
dc.relation.isbasedonWOS:000379484601161
dc.titleTriggering the TCR developmental checkpoin activates a therapeutically targetable tumor suppressive pathway in T-cell leukemia
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F04773%2F2013/PT
oaire.citation.conferencePlaceCopenhagen, Denmark
oaire.citation.endPage322
oaire.citation.startPage321
oaire.citation.titleHaematologica
oaire.citation.volume101
oaire.fundingStream5876
person.familyNameRodrigues dos Santos
person.givenNameNuno
person.identifier.orcid0000-0001-7347-2592
person.identifier.scopus-author-id7006810054
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublicationcd54e8ca-80e4-49d1-8fa1-d275fc51ddb2
relation.isAuthorOfPublication.latestForDiscoverycd54e8ca-80e4-49d1-8fa1-d275fc51ddb2
relation.isProjectOfPublicatione13142f2-37b8-4b5a-b2cd-352e62003184
relation.isProjectOfPublication.latestForDiscoverye13142f2-37b8-4b5a-b2cd-352e62003184

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
972.full.pdf
Size:
29.55 MB
Format:
Adobe Portable Document Format
Download

Collections

FCB2-Artigos (em revistas ou actas indexadas)