Pan-SRC kinase inhibition blocks B-cell receptor oncogenic signaling in non-Hodgkin lymphoma.

Détails

ID Serval
serval:BIB_628039C698E5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Pan-SRC kinase inhibition blocks B-cell receptor oncogenic signaling in non-Hodgkin lymphoma.
Périodique
Blood
Auteur(s)
Battistello E., Katanayeva N., Dheilly E., Tavernari D., Donaldson M.C., Bonsignore L., Thome M., Christie A.L., Murakami M.A., Michielin O., Ciriello G., Zoete V., Oricchio E.
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Statut éditorial
Publié
Date de publication
24/05/2018
Peer-reviewed
Oui
Volume
131
Numéro
21
Pages
2345-2356
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
In diffuse large B-cell lymphoma (DLBCL), activation of the B-cell receptor (BCR) promotes multiple oncogenic signals, which are essential for tumor proliferation. Inhibition of the Bruton's tyrosine kinase (BTK), a BCR downstream target, is therapeutically effective only in a subgroup of patients with DLBCL. Here, we used lymphoma cells isolated from patients with DLBCL to measure the effects of targeted therapies on BCR signaling and to anticipate response. In lymphomas resistant to BTK inhibition, we show that blocking BTK activity enhanced tumor dependencies from alternative oncogenic signals downstream of the BCR, converging on MYC upregulation. To completely ablate the activity of the BCR, we genetically and pharmacologically repressed the activity of the SRC kinases LYN, FYN, and BLK, which are responsible for the propagation of the BCR signal. Inhibition of these kinases strongly reduced tumor growth in xenografts and cell lines derived from patients with DLBCL independent of their molecular subtype, advancing the possibility to be relevant therapeutic targets in broad and diverse groups of DLBCL patients.
Mots-clé
Animals, Cell Line, Tumor, Cell Transformation, Neoplastic/metabolism, Disease Models, Animal, Drug Resistance, Neoplasm/genetics, Gene Expression, Genes, myc, Humans, Lymphoma, Non-Hodgkin/drug therapy, Lymphoma, Non-Hodgkin/etiology, Lymphoma, Non-Hodgkin/metabolism, Lymphoma, Non-Hodgkin/pathology, Mice, Mice, Knockout, Protein Kinase Inhibitors/pharmacology, Pyrazoles/pharmacology, Pyrimidines/pharmacology, Receptors, Antigen, B-Cell/metabolism, Signal Transduction/drug effects, Xenograft Model Antitumor Assays, src-Family Kinases/antagonists & inhibitors
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/03/2018 19:38
Dernière modification de la notice
20/08/2019 14:19
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