B-cell receptor-driven MALT1 activity regulates MYC signaling in mantle cell lymphoma.

Détails

Ressource 1Télécharger: 5_27864294_Postprint.pdf (2306.78 [Ko])
Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_4B730E70EDA4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
B-cell receptor-driven MALT1 activity regulates MYC signaling in mantle cell lymphoma.
Périodique
Blood
Auteur(s)
Dai B., Grau M., Juilland M., Klener P., Höring E., Molinsky J., Schimmack G., Aukema S.M., Hoster E., Vogt N., Staiger A.M., Erdmann T., Xu W., Erdmann K., Dzyuba N., Madle H., Berdel W.E., Trneny M., Dreyling M., Jöhrens K., Lenz P., Rosenwald A., Siebert R., Tzankov A., Klapper W., Anagnostopoulos I., Krappmann D., Ott G., Thome M., Lenz G.
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Statut éditorial
Publié
Date de publication
19/01/2017
Peer-reviewed
Oui
Volume
129
Numéro
3
Pages
333-346
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Mantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by poor clinical outcome. Recent studies revealed the importance of B-cell receptor (BCR) signaling in maintaining MCL survival. However, it remains unclear which role MALT1, an essential component of the CARD11-BCL10-MALT1 complex that links BCR signaling to the NF-κB pathway, plays in the biology of MCL. Here we show that a subset of MCLs is addicted to MALT1, as its inhibition by either RNA or pharmacologic interference induced cytotoxicity both in vitro and in vivo. Gene expression profiling following MALT1 inhibition demonstrated that MALT1 controls an MYC-driven gene expression network predominantly through increasing MYC protein stability. Thus, our analyses identify a previously unappreciated regulatory mechanism of MYC expression. Investigating primary mouse splenocytes, we could demonstrate that MALT1-induced MYC regulation is not restricted to MCL, but represents a common mechanism. MYC itself is pivotal for MCL survival because its downregulation and pharmacologic inhibition induced cytotoxicity in all MCL models. Collectively, these results provide a strong mechanistic rationale to investigate the therapeutic efficacy of targeting the MALT1-MYC axis in MCL patients.

Pubmed
Web of science
Open Access
Oui
Création de la notice
05/12/2016 21:45
Dernière modification de la notice
20/08/2019 13:59
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