Search

Your search keyword '"Machiorlatti R"' showing total 3 results
Start Over Author "Machiorlatti R" Topic lymphoma, large-cell, anaplastic
3 results on '"Machiorlatti R"'

1. Identification of a new subclass of ALK-negative ALCL expressing aberrant levels of ERBB4 transcripts.

Author

Scarfò I, Pellegrino E, Mereu E, Kwee I, Agnelli L, Bergaggio E, Garaffo G, Vitale N, Caputo M, Machiorlatti R, Circosta P, Abate F, Barreca A, Novero D, Mathew S, Rinaldi A, Tiacci E, Serra S, Deaglio S, Neri A, Falini B, Rabadan R, Bertoni F, Inghirami G, and Piva R

Subjects
5' Untranslated Regions, Anaplastic Lymphoma Kinase, Animals, Codon, Nonsense, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Lymphoma, Large-Cell, Anaplastic classification, Lymphoma, Large-Cell, Anaplastic pathology, Mice, Mice, Inbred NOD, Mice, SCID, Mice, Transgenic, Molecular Sequence Data, Mutant Proteins genetics, Mutant Proteins metabolism, NIH 3T3 Cells, RNA, Messenger metabolism, Receptor Protein-Tyrosine Kinases metabolism, Receptor, ErbB-4 metabolism, Lymphoma, Large-Cell, Anaplastic genetics, Receptor Protein-Tyrosine Kinases genetics, Receptor, ErbB-4 genetics
Abstract

Anaplastic large-cell lymphoma (ALCL) is a clinical and biological heterogeneous disease that includes systemic anaplastic lymphoma kinase (ALK)-positive and ALK-negative entities. To discover biomarkers and/or genes involved in ALK-negative ALCL pathogenesis, we applied the cancer outlier profile analysis algorithm to a gene expression profiling data set including 249 cases of T-cell non-Hodgkin lymphoma and normal T cells. Ectopic coexpression of ERBB4 and COL29A1 genes was detected in 24% of ALK-negative ALCL patients. RNA sequencing and 5' RNA ligase-mediated rapid amplification of complementary DNA ends identified 2 novel ERBB4-truncated transcripts displaying intronic transcription start sites. By luciferase assays, we defined that the expression of ERBB4-aberrant transcripts is promoted by endogenous intronic long terminal repeats. ERBB4 expression was confirmed at the protein level by western blot analysis and immunohistochemistry. Lastly, we demonstrated that ERBB4-truncated forms show oncogenic potentials and that ERBB4 pharmacologic inhibition partially controls ALCL cell growth and disease progression in an ERBB4-positive patient-derived tumorgraft model. In conclusion, we identified a new subclass of ALK-negative ALCL characterized by aberrant expression of ERBB4-truncated transcripts carrying intronic 5' untranslated regions., (© 2016 by The American Society of Hematology.)

Published
2016
Full Text
View/download PDF

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

Author

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, and Inghirami G

Subjects
Anaplastic Lymphoma Kinase, Animals, Blotting, Western, 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 mortality, Mice, Mice, Inbred NOD, NF-kappa B genetics, Positive Regulatory Domain I-Binding Factor 1, 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 metabolism, Repressor Proteins genetics, Repressor Proteins metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, TNF Receptor-Associated Factor 1 metabolism, Tumor Cells, Cultured, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Xenograft Model Antitumor Assays, Drug Resistance, Neoplasm, Lymphoma, Large-Cell, Anaplastic genetics, NF-kappa B metabolism, Receptor Protein-Tyrosine Kinases genetics, TNF Receptor-Associated Factor 1 genetics, Translocation, Genetic genetics
Abstract

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.

Published
2015
Full Text
View/download PDF

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

Author

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, 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, and andThe European T-cell Lymphoma Study, Group

Subjects
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
Abstract

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.

Published
2015

Catalog

Books, media, physical & digital resources
See catalog results