A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation
| Autor: | Thomas Tousseyn, Elena Lasorsa, M. Ponzoni, Cristina Abele, Andrea Acquaviva, S. A. Pileri, Pier Paolo Piccaluga, Domenico Novero, Maria Todaro, Antonella Barreca, Francesco Abate, Ivo Kwee, Giorgio Inghirami, F Di Giacomo, Javeed Iqbal, Indira Landra, Raul Rabadan, Silvio Aime, Wing C. Chan, Rodolfo Machiorlatti, Mangeng Cheng, Michela Boi, Enrico Tiacci, B Pera-Gresely, Francesco Bertoni, Leonard D. Shultz, J-A van der Krogt, Katia Messana, Bruce Ruggeri, Brunangelo Falini, Sabrina Aliberti, Fabrizio Tabbò, Marcello Gaudiano, Luca Bessone, Roberto Piva, R Crescenzo, Andrea Rinaldi, Iwona Wlodarska, Dario Livio Longo, Elisa Ficarra, Leandro Cerchietti |
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| Přispěvatelé: | 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., The European T-cell Lymphoma Study Group [.., Agostinelli, C., ], European T-cell Lymphoma Study Group, Cavallo, F., Chiesa, N., Fienga, A., di Giacomo, F., Marchiorlatti, R., Martinoglio, B., Medico, E., Ferrero, GB., Mereu, E., Pellegrino, E., Scafò, I., Spaccarotella, E., Ubezzi, I., Urigu, S., Chiapella, A., Vitolo, U., Agnelli, L., Neri, A., Chilosi£££Anna Caliò Marco£££ AC., Zamó, A., Facchetti, F., Lonardi, S., De Chiara, A., Fulciniti, F., Ferreri, A., Piccaluga, PP., Van Loo, P., De Wolf-Peeters, C., Geissinger, E., Muller-Hermelink, HK., Rosenwald, A., Piris, MA., Rodriguez, ME., Chiattone, C., Paes, RA., Abate, F, Todaro, M, van der Krogt, Ja, 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, Dl, Aime, S, Cheng, M, Ruggeri, B, Piccaluga, Pp, Pileri, S, Tiacci, E, Falini, B, Pera-Gresely, B, Cerchietti, L, Iqbal, J, Chan, Wc, Shultz, Ld, Kwee, I, Piva, R, Wlodarska, I, Rabadan, R, Bertoni, F, Inghirami, G, andThe European T-cell Lymphoma Study, Group |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Pathology
Cancer Research Lymphoma TRAF1 Messenger Drug Resistance Translocation Genetic Fusion gene Mice Mice Inbred NOD hemic and lymphatic diseases Tumor Cells Cultured Anaplastic lymphoma kinase Anaplastic Anaplastic Lymphoma Kinase Anaplastic large-cell lymphoma Animals Blotting Western Flow Cytometry Gene Expression Profiling High-Throughput Nucleotide Sequencing Humans Immunoprecipitation In Situ Hybridization Fluorescence Lymphoma Large-Cell Anaplastic NF-kappa B Proteasome Inhibitors Proto-Oncogene Proteins c-myc RNA Messenger Real-Time Polymerase Chain Reaction Receptor Protein-Tyrosine Kinases Repressor Proteins Reverse Transcriptase Polymerase Chain Reaction Signal Transduction TNF Receptor-Associated Factor 1 Tumor Suppressor Protein p53 Xenograft Model Antitumor Assays Drug Resistance Neoplasm In Situ Hybridization Hematology Cultured Blotting Medicine (all) Large-Cell Tumor Cells Proteasome Inhibitor Receptor Protein-Tyrosine Kinase Oncology Western Human medicine.medical_specialty fusion detection tool Xenograft Model Antitumor Assay medicine.drug_class Translocation Anesthesiology and Pain Medicine Biology anaplastic large-cell lymphomas (ALCL) RNA-Seq data Fluorescence Article Genetic Internal medicine PRDM1 medicine traslocation Animal Repressor Protein medicine.disease ALK inhibitor anaplastic lymphoma kinase (ALK) Cancer research Inbred NOD RNA Neoplasm Positive Regulatory Domain I-Binding Factor 1 Lymphoma Large-Cell Anaplastic/drug therapy Lymphoma Large-Cell Anaplastic/genetics 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 Receptor Protein-Tyrosine Kinases/genetics Receptor Protein-Tyrosine Kinases/metabolism Repressor Proteins/genetics Repressor Proteins/metabolism TNF Receptor-Associated Factor 1/genetics TNF Receptor-Associated Factor 1/metabolism Translocation Genetic/genetics Tumor Suppressor Protein p53/genetics Tumor Suppressor Protein p53/metabolism |
| Zdroj: | Leukemia, vol. 29, no. 6, pp. 1390-1401 |
| Popis: | 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 kappa B (NF kappa B) 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 NF kappa B 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 NF kappa B 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. |
| Databáze: | OpenAIRE |
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