A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation.

Détails

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_0D92E89F5C27
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation.
Périodique
Leukemia
Auteur(s)
Abate F., Todaro M., van der Krogt J.A., Boi M., Landra I., Machiorlatti R., Tabbò F., Messana K., Abele C., Barreca A., Novero D., Gaudiano M., Aliberti S., Di Giacomo F., Tousseyn T., Lasorsa E., Crescenzo R., Bessone L., Ficarra E., Acquaviva A., Rinaldi A., Ponzoni M., Longo D.L., Aime S., Cheng M., Ruggeri B., Piccaluga P.P., Pileri S., Tiacci E., Falini B., Pera-Gresely B., Cerchietti L., Iqbal J., Chan W.C., Shultz L.D., Kwee I., Piva R., Wlodarska I., Rabadan R., Bertoni F., Inghirami G.
Collaborateur(s)
European T-cell Lymphoma Study Group
Contributeur(s)
Abele C., Bessone L., Barreca A., Boi M., Cavallo F., Chiesa N., Crescenzo R., Fienga A., Gaudiano M., di Giacomo F., Inghirami G., Landra I., Lasorsa E., Marchiorlatti R., Martinoglio B., Medico E., Ferrero GB., Messana K., Mereu E., Pellegrino E., Piva R., Scafò I., Spaccarotella E., Tabbò F., Todaro M., Ubezzi I., Urigu S., Novero D., Chiapella A., Vitolo U., Abate F., Ficarra E., Acquaviva A., Agnelli L., Neri A., Chilosi£££Anna Caliò Marco£££ AC. , Zamó A., Facchetti F., Lonardi S., De Chiara A., Fulciniti F., Ferreri A., Ponzoni M., Agostinelli C., Piccaluga PP., Pileri S., Falini B., Tiacci E., Van Loo P., Tousseyn T., De Wolf-Peeters C., Geissinger E., Muller-Hermelink HK., Rosenwald A., Piris MA., Rodriguez ME., Bertoni F., Rinaldi A., Kwee I., Chiattone C., Paes RA.
ISSN
1476-5551 (Electronic)
ISSN-L
0887-6924
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
29
Numéro
6
Pages
1390-1401
Langue
anglais
Résumé
Although anaplastic large-cell lymphomas (ALCL) carrying anaplastic lymphoma kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human patient-derived tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and nuclear factor kB (NFkB) pathways. Genomic studies of ALCL-11 showed the TP53 loss and the in vivo subclonal expansion of lymphoma cells, lacking PRDM1/Blimp1 and carrying c-MYC gene amplification. The treatment with proteasome inhibitors of TRAF1-ALK cells led to the downregulation of p50/p52 and lymphoma growth inhibition. Moreover, a NFkB gene set classifier stratified ALCL in distinct subsets with different clinical outcome. Although a selective ALK inhibitor (CEP28122) resulted in a significant clinical response of hPDT mice, nevertheless the disease could not be eradicated. These data indicate that the activation of NFkB signaling contributes to the neoplastic phenotype of TRAF1-ALK ALCL. ALCL hPDTs are invaluable tools to validate the role of druggable molecules, predict therapeutic responses and implement patient specific therapies.
Mots-clé
Animals, Blotting, Western, Drug Resistance, Neoplasm, Flow Cytometry, Gene Expression Profiling, High-Throughput Nucleotide Sequencing, Humans, Immunoprecipitation, In Situ Hybridization, Fluorescence, Lymphoma, Large-Cell, Anaplastic/drug therapy, Lymphoma, Large-Cell, Anaplastic/genetics, Mice, Mice, Inbred NOD, NF-kappa B/genetics, NF-kappa B/metabolism, Proteasome Inhibitors/pharmacology, Proto-Oncogene Proteins c-myc/genetics, Proto-Oncogene Proteins c-myc/metabolism, RNA, Messenger/genetics, Real-Time Polymerase Chain Reaction, Receptor Protein-Tyrosine Kinases/genetics, Receptor Protein-Tyrosine Kinases/metabolism, Repressor Proteins/genetics, Repressor Proteins/metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, TNF Receptor-Associated Factor 1/genetics, TNF Receptor-Associated Factor 1/metabolism, Translocation, Genetic/genetics, Tumor Cells, Cultured, Tumor Suppressor Protein p53/genetics, Tumor Suppressor Protein p53/metabolism, Xenograft Model Antitumor Assays
Pubmed
Web of science
Création de la notice
25/11/2015 17:17
Dernière modification de la notice
03/03/2018 13:40
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