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1. Frequent mutations of FBXO11 highlight BCL6 as a therapeutic target in Burkitt lymphoma

Author

Pighi, Chiara, Cheong, Taek-Chin, Compagno, Mara, Patrucco, Enrico, Arigoni, Maddalena, Olivero, Martina, Wang, Qi, López, Cristina, Bernhart, Stephan H., Grande, Bruno M., Poggio, Teresa, Langellotto, Fernanda, Bonello, Lisa, Dall'Olio, Riccardo, Martínez-Martín, Sandra, Molinaro, Luca, Francia di Celle, Paola, Whitfield, Jonathan R., Soucek, Laura, Voena, Claudia, Calogero, Raffaele A., Morin, Ryan D., Staudt, Louis M., Siebert, Reiner, Zamò, Alberto, and Chiarle, Roberto

Published
2021
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3. P606: MEASUREMENT OF INTRACLONAL DIVERSIFICATION REFINES THE PROGNOSTIC IMPACT OF IGHV MUTATIONS IN CLL

Author

Vit, Filippo, primary, Bittolo, Tamara, additional, Papotti, Robel, additional, Pozzo, Federico, additional, Zucchetto, Antonella, additional, Tissino, Erika, additional, Zaina, Eva, additional, Catarossi, Ilaria, additional, Laureana, Roberta, additional, Olivieri, Jacopo, additional, Bulian, Pietro, additional, Levato, Luciano, additional, D’arena, Giovanni, additional, Armiento, Daniele, additional, Zamò, Alberto, additional, Leich, Ellen, additional, Rosenwald, Andreas, additional, Arons, Evgeny, additional, J. Kreitman, Robert, additional, Gentile, Massimo, additional, Laurenti, Luca, additional, Zaja, Francesco, additional, Tafuri, Agostino, additional, Chiarenza, Annalisa, additional, Ilaria DEL Principe, Maria, additional, Gattei, Valter, additional, and Bomben, Riccardo, additional

Published
2023
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4. P1208: TRANSCRIPTOMIC PROFILING OF B CELL STATES AND MICROENVIROMENTAL ECOSYSTEMS REFINES THE PROGNOSTIC CLASSIFICATION OF DIFFUSE LARGE B CELL LYMPHOMA

Author

Papotti, Robel, primary, Vit, Filippo, additional, Pozzo, Federico, additional, Bittolo, Tamara, additional, Bettelli, Stefania, additional, Pozzi, Samantha, additional, Maiorana, Antonino, additional, Forti, Elisa, additional, Napoli, Arianna DI, additional, Christina Cox, Maria, additional, Tadmor, Tamar, additional, Mansueto, Giovanna, additional, Musto, Pellegrino, additional, Flenghi, Leonardo, additional, Quintini, Martina, additional, Lalinga, Vittoria, additional, Galimberti, Sara, additional, Donati, Valentina, additional, Spina, Michele, additional, Zamò, Alberto, additional, Rosenwald, Andreas, additional, Bomben, Riccardo, additional, Sacchi, Stefano, additional, and Gattei, Valter, additional

Published
2023
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5. ESMO Consensus Conference on malignant lymphoma: general perspectives and recommendations for the clinical management of the elderly patient with malignant lymphoma

Author

Buske, Christian, Dreyling, Martin, Ferreri, Andrés J M, Fields, Paul, Gaidano, Gianluca, Goede, Valentin, Hutchings, Martin, Ladetto, Marco, Le Gouill, Steven, Luminari, Stefano, Mey, Ulrich, de Nully Brown, Peter, Pfreundschuh, Michael, Pott, Christiane, Schmitz, Norbert, Soubeyran, Pierre, Spina, Michele, Stauder, Reinhard, Balari, Anna Sureda, Trněný, Marek, van Imhoff, Gustaaf, Walewski, Jan, Wedding, Ulrich, Zamò, Alberto, Zucca, Emanuele, Buske, C., Hutchings, M., Ladetto, M., Goede, V., Mey, U., Soubeyran, P., Spina, M., Stauder, R., Trněný, M., Wedding, U., and Fields, P.

Published
2018
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6. Targeted panel sequencing in the routine diagnosis of mature T- and NK-cell lymphomas: report of 128 cases from two German reference centers.

Author

Böck, Julia, Maurus, Katja, Gerhard-Hartmann, Elena, Brändlein, Stephanie, Kurz, Katrin S., Ott, German, Anagnostopoulos, Ioannis, Rosenwald, Andreas, and Zamò, Alberto

Subjects
LYMPHOMAS, T-cell lymphoma, T cells, PROGNOSIS, FLOW cytometry
Abstract

Diagnosing any of the more than 30 types of T-cell lymphomas is considered a challenging task for many pathologists and currently requires morphological expertise as well as the integration of clinical data, immunophenotype, flow cytometry and clonality analyses. Even considering all available information, some margin of doubt might remain using the current diagnostic procedures. In recent times, the genetic landscape of most T-cell lymphomas has been elucidated, showing a number of diagnostically relevant mutations. In addition, recent data indicate that some of these genetic alterations might bear prognostic and predictive value. Extensive genetic analyses, such as whole exome or large panel sequencing are still expensive and time consuming, therefore limiting their application in routine diagnostic. We therefore devoted our effort to develop a lean approach for genetic analysis of T-cell lymphomas, focusing on maximum efficiency rather than exhaustively covering all possible targets. Here we report the results generated with our small amplicon-based panel that could be used routinely on paraffin-embedded and even decalcified samples, on a single sample basis in parallel with other NGS-panels used in our routine diagnostic lab, in a relatively short time and with limited costs. We tested 128 available samples from two German reference centers as part of our routine work up (among which 116 T-cell lymphomas), which is the largest routine diagnostic series reported to date. Our results showed that this assay had a very high rate of technical success (97%) and could detect mutations in the majority (79%) of tested T-cell lymphoma samples. [ABSTRACT FROM AUTHOR]

Published
2023
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7. DNA methylation profiling identifies two splenic marginal zone lymphoma subgroups with different clinical and genetic features

Author

Arribas, Alberto J., Rinaldi, Andrea, Mensah, Afua A., Kwee, Ivo, Cascione, Luciano, Robles, Eloy F., Martinez-Climent, Jose A., Oscier, David, Arcaini, Luca, Baldini, Luca, Marasca, Roberto, Thieblemont, Catherine, Briere, Josette, Forconi, Francesco, Zamò, Alberto, Bonifacio, Massimiliano, Mollejo, Manuela, Facchetti, Fabio, Dirnhofer, Stephan, Ponzoni, Maurilio, Bhagat, Govind, Piris, Miguel A., Gaidano, Gianluca, Zucca, Emanuele, Rossi, Davide, and Bertoni, Francesco

Published
2015
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9. Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome

Author

Chigrinova, Ekaterina, Rinaldi, Andrea, Kwee, Ivo, Rossi, Davide, Rancoita, Paola M.V., Strefford, Jonathan C., Oscier, David, Stamatopoulos, Kostas, Papadaki, Theodora, Berger, Francoise, Young, Ken H., Murray, Fiona, Rosenquist, Richard, Greiner, Timothy C., Chan, Wing C., Orlandi, Ester M., Lucioni, Marco, Marasca, Roberto, Inghirami, Giorgio, Ladetto, Marco, Forconi, Francesco, Cogliatti, Sergio, Votavova, Hana, Swerdlow, Steven H., Stilgenbauer, Stephan, Piris, Miguel A., Matolcsy, Andras, Spagnolo, Dominic, Nikitin, Eugene, Zamò, Alberto, Gattei, Valter, Bhagat, Govind, Ott, German, Zucca, Emanuele, Gaidano, Gianluca, and Bertoni, Francesco

Published
2013
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10. Case Report: Sequential Development of Three Mature Lymphoid Neoplasms in a Single Patient: Clonal Relationship and Molecular Insights

Author

Salvetti, Chiara, Vitale, Candida, Griggio, Valentina, Drandi, Daniela, Jones, Rebecca, Bonello, Lisa, Bomben, Riccardo, Bragoni, Alberto, Bagnara, Davide, Fais, Franco, Gattei, Valter, Cavallo, Federica, Zamò, Alberto, and Coscia, Marta

Subjects
Hodgkin lymphoma, IGHV genes, Richter’s syndrome, chronic lymphocytic leukemia, monoclonal B-cell lymphocytosis, Cancer Research, Oncology
Abstract

Two main variants of Richter syndrome (RS) are recognized, namely, the diffuse large B-cell lymphoma (DLBCL) and the Hodgkin’s lymphoma (HL) variant. Clonal relationship, defined as an identity of the immunoglobulin heavy chain variable (IGHV) region sequence between chronic lymphocytic leukemia (CLL) and RS clones, characterizes patients with a poor prognosis. Due to method sensitivity, this categorization is performed without considering the possibility of small-size ancillary clones, sharing the same phenotype with the preexisting predominant CLL clone, but with different IGHV rearrangements. Here we describe and molecularly profile the peculiar case of a patient with a CLL-like monoclonal B-cell lymphocytosis (MBL), who sequentially developed a DLBCL, which occurred concomitantly to progression of MBL to CLL, and a subsequent HL. Based on standard IGHV clonality analysis, DLBCL was considered clonally unrelated to the concomitantly expanded CLL clone and treated as a de novo lymphoma, achieving a persistent response. Three years later, the patient further developed a clonally unrelated HL, refractory to bendamustine, which was successfully treated with brentuximab vedotin and radiotherapy, and later with pembrolizumab. We retrospectively performed additional molecular testing, by applying next-generation sequencing (NGS) of immunoglobulin repertoire (Ig-rep) techniques and a more sensitive allele-specific oligonucleotide-droplet digital PCR (ASO-ddPCR) strategy, in order to quantitatively investigate the presence of the rearranged IGHV genes in tumor specimens collected during the disease course. In this highly complex case, the application of modern and sensitive molecular technologies uncovered that DLBCL, initially considered as a de novo lymphoma, was instead the result of the transformation of a preexisting ancillary B-cell clone, which was already present at the time of first MBL diagnosis. A similar approach was also applied on the HL sample, showing its clonal unrelatedness to the previous MBL and DLBCL.

Published
2022

11. Deep Neural Networks and Machine Learning Radiomics Modelling for Prediction of Relapse in Mantle Cell Lymphoma

Author

Lisson, Catharina Silvia, Lisson, Christoph Gerhard, Mezger, Marc Fabian, Wolf, Daniel, Schmidt, Stefan Andreas, Thaiss, Wolfgang M., Tausch, Eugen, Beer, Ambros J., Stilgenbauer, Stephan, Beer, Meinrad, Goetz, Michael, and Zamò, Alberto

Subjects
personalised oncology, Cancer Research, radiomics, machine learning, deep learning, deep neural networks, precision imaging, Deep Learning, Oncology, Machine learning, ddc:000, Diagnostic imaging, ddc:610, DDC 000 / Computer science, information & general works, DDC 610 / Medicine & health, Maschinelles Lernen
Abstract

Simple Summary Mantle cell lymphoma (MCL) is an aggressive lymphoid tumour with a poor prognosis. There exist no routine biomarkers for the early prediction of relapse. Our study compared the potential of radiomics-based machine learning and 3D deep learning models as non-invasive biomarkers to risk-stratify MCL patients, thus promoting precision imaging in clinical oncology. Abstract Mantle cell lymphoma (MCL) is a rare lymphoid malignancy with a poor prognosis characterised by frequent relapse and short durations of treatment response. Most patients present with aggressive disease, but there exist indolent subtypes without the need for immediate intervention. The very heterogeneous behaviour of MCL is genetically characterised by the translocation t(11;14)(q13;q32), leading to Cyclin D1 overexpression with distinct clinical and biological characteristics and outcomes. There is still an unfulfilled need for precise MCL prognostication in real-time. Machine learning and deep learning neural networks are rapidly advancing technologies with promising results in numerous fields of application. This study develops and compares the performance of deep learning (DL) algorithms and radiomics-based machine learning (ML) models to predict MCL relapse on baseline CT scans. Five classification algorithms were used, including three deep learning models (3D SEResNet50, 3D DenseNet, and an optimised 3D CNN) and two machine learning models based on K-nearest Neighbor (KNN) and Random Forest (RF). The best performing method, our optimised 3D CNN, predicted MCL relapse with a 70% accuracy, better than the 3D SEResNet50 (62%) and the 3D DenseNet (59%). The second-best performing method was the KNN-based machine learning model (64%) after principal component analysis for improved accuracy. Our optimised CNN developed by ourselves correctly predicted MCL relapse in 70% of the patients on baseline CT imaging. Once prospectively tested in clinical trials with a larger sample size, our proposed 3D deep learning model could facilitate clinical management by precision imaging in MCL., publishedVersion

Published
2022

14. B-cell receptor signaling and genetic lesions in TP53 and CDKN2A/CDKN2B cooperate in Richter transformation

Author

Chakraborty, Supriya, primary, Martines, Claudio, additional, Porro, Fabiola, additional, Fortunati, Ilaria, additional, Bonato, Alice, additional, Dimishkovska, Marija, additional, Piazza, Silvano, additional, Yadav, Brijesh S., additional, Innocenti, Idanna, additional, Fazio, Rosa, additional, Vaisitti, Tiziana, additional, Deaglio, Silvia, additional, Zamò, Alberto, additional, Dimovski, Aleksandar J., additional, Laurenti, Luca, additional, and Efremov, Dimitar G., additional

Published
2021
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16. Droplet Digital PCR Assay for MYD88L265P

Author

Lo Schirico, Mariella, Ferrante, Martina, Dogliotti, Irene, Zamò, Alberto, Ferrero, Bruno, Bertuzzo, Davide, Benevolo, Giulia, Omedè, Paola, Cavallo, Federica, Ladetto, Marco, Boccadoro, Mario, Drandi, Daniela, and Ferrero, Simone

Published
2020

19. Combined Genetic Lesions in TP53 and CDKN2A/CDKN2B Drive B Cell Receptor-Dependent/Costimulatory Signal-Independent Proliferation in Richter Syndrome

Author

Chakraborty, Supriya, primary, Martines, Claudio, additional, Porro, Fabiola, additional, Fortunati, Ilaria, additional, Bonato, Alice, additional, Dimishkovska, Marija, additional, Yadav, Brijesh, additional, Innocenti, Idanna, additional, Fazio, Rosa, additional, Vaisitti, Tizianna, additional, Deaglio, Silvia, additional, Zamò, Alberto, additional, Dimovski, Aleksandar, additional, Laurenti, Luca, additional, and Efremov, Dimitar G, additional

Published
2020
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20. Identification of a new subclass of ALK-negative ALCL expressing aberrant levels of ERBB4 transcripts

Author

Scarfò, Irene, Pellegrino, Elisa, Mereu, Elisabetta, Kwee, Ivo, Agnelli, Luca, Bergaggio, Elisa, Garaffo, Giulia, Vitale, Nicoletta, Caputo, Manuel, Machiorlatti, Rodolfo, Circosta, Paola, Abate, Francesco, Barreca, Antonella, Novero, Domenico, Mathew, Susan, Rinaldi, Andrea, Tiacci, Enrico, Serra, Sara, Deaglio, Silvia, Neri, Antonino, Falini, Brunangelo, Rabadan, Raul, Bertoni, Francesco, Inghirami, Giorgio, Piva, Roberto, Boi, Michela, Crescenzo, Ramona, Cuccuru, Giuditta, Gaudiano, Marcello, Lasorsa, Elena, Medico, Enzo, Messana, Katia, Spaccarotella, Elisa, Tabbò, Fabrizio, Todaro, Maria, Fornari, Alessandro, Chilosi, Marco, Zamò, Alberto, Facchetti, Fabio, Lonardi, Silvia, De Chiara, Anna, Fulciniti, Franco, Doglioni, Claudio, Ponzoni, Maurilio, Todoerti, Katia, De Wolf Peeters, Christiane, Tousseyn, Thomas, Van Loo, Peter, Geissinger, Eva, Muller Hermelink, Hans Konrad, Rosenwald, Andreas, Matolcsy, Andras, Piris, Miguel Angel, Rodriguez Pinilla, Maria E., AGOSTINELLI, CLAUDIO, PICCALUGA, PIER PAOLO, PILERI, STEFANO, Scarfò, Irene, Pellegrino, Elisa, Mereu, Elisabetta, Kwee, Ivo, Agnelli, Luca, Bergaggio, Elisa, Garaffo, Giulia, Vitale, Nicoletta, Caputo, Manuel, Machiorlatti, Rodolfo, Circosta, Paola, Abate, Francesco, Barreca, Antonella, Novero, Domenico, Mathew, Susan, Rinaldi, Andrea, Tiacci, Enrico, Serra, Sara, Deaglio, Silvia, Neri, Antonino, Falini, Brunangelo, Rabadan, Raul, Bertoni, Francesco, Inghirami, Giorgio, Piva, Roberto, Boi, Michela, Crescenzo, Ramona, Cuccuru, Giuditta, Gaudiano, Marcello, Lasorsa, Elena, Medico, Enzo, Messana, Katia, Spaccarotella, Elisa, Tabbò, Fabrizio, Todaro, Maria, Fornari, Alessandro, Chilosi, Marco, Zamò, Alberto, Facchetti, Fabio, Lonardi, Silvia, De Chiara, Anna, Fulciniti, Franco, Doglioni, Claudio, Ponzoni, Maurilio, Todoerti, Katia, Agostinelli, Claudio, Piccaluga, Pier Paolo, Pileri, Stefano, De Wolf-Peeters, Christiane, Tousseyn, Thoma, Van Loo, Peter, Geissinger, Eva, Muller-Hermelink, Hans Konrad, Rosenwald, Andrea, Matolcsy, Andra, Piris, Miguel Angel, Rodriguez-Pinilla, Maria E., 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, Piva, R, the European T-Cell Lymphoma Study, Group, Doglioni, C, and Ponzoni, M

Subjects
0301 basic medicine, Untranslated region, Receptor, ErbB-4, Messenger, Mice, SCID, Biochemistry, Mice, 0302 clinical medicine, 5' Untranslated Region, HEK293 Cell, Mutant Protein, Mice, Inbred NOD, hemic and lymphatic diseases, 5' Untranslated RegionsAnimalsCodon, Anaplastic lymphoma kinase, Anaplastic Lymphoma Kinase, NIH 3T3 Cell, Regulation of gene expression, TransgenicMolecular Sequence DataMutant ProteinsNIH 3T3 CellsReceptor Protein-Tyrosine KinasesReceptor, Hematology, Long terminal repeat, Large-Cell, Gene Expression Regulation, Neoplastic, Receptor Protein-Tyrosine Kinase, Codon, Nonsense, 030220 oncology & carcinogenesis, Lymphoma, Large-Cell, Anaplastic, Human, Molecular Sequence Data, Immunology, ErbB-4RNA, Mice, Transgenic, Biology, 03 medical and health sciences, Complementary DNA, Animals, Humans, RNA, Messenger, Gene, NonsenseGene Expression Regulation, NeoplasticHEK293 CellsHumansLymphoma, Animal, Receptor Protein-Tyrosine Kinases, RNA, Cell Biology, Molecular biology, Gene expression profiling, HEK293 Cells, 030104 developmental biology, Inbred NODMice, NIH 3T3 Cells, Mutant Proteins, SCIDMice, AnaplasticMiceMice, 5' Untranslated Regions, 5' Untranslated RegionsAnimalsCodon, NonsenseGene Expression Regulation, NeoplasticHEK293 CellsHumansLymphoma, Large-Cell, AnaplasticMiceMice, Inbred NODMice, SCIDMice, TransgenicMolecular Sequence DataMutant ProteinsNIH 3T3 CellsReceptor Protein-Tyrosine KinasesReceptor, ErbB-4RNA, Messenger
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

21. Intensive short-term chemotherapy regimen induces high remission rate (over 90%) and event-free survival both in children and adult patients with advanced sporadic Burkitt lymphoma/leukemia

Author

Todeschini, Giuseppe, Bonifacio, Massimiliano, Tecchio, Cristina, Balter, Rita, Carli, Giuseppe, Stefani, Piero Maria, Adami, Fausto, Zamò, Alberto, Tos, Angelo Paolo Dei, Marino, Filippo, Gherlinzoni, Filippo, Marradi, Pierluigi, Semenzato, Giampietro, and Pizzolo, Giovanni

Published
2012
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22. Droplet Digital PCR Assay for MYD88 L265P : Clinical Applications in Waldenström Macroglobulinemia

Author

Lo Schirico, Mariella, primary, Ferrante, Martina, additional, Dogliotti, Irene, additional, Zamò, Alberto, additional, Ferrero, Bruno, additional, Bertuzzo, Davide, additional, Benevolo, Giulia, additional, Omedè, Paola, additional, Cavallo, Federica, additional, Ladetto, Marco, additional, Boccadoro, Mario, additional, Drandi, Daniela, additional, and Ferrero, Simone, additional

Published
2020
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26. KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study

Author

Ferrero, Simone, primary, Rossi, Davide, additional, Rinaldi, Andrea, additional, Bruscaggin, Alessio, additional, Spina, Valeria, additional, Eskelund, Christian W., additional, Evangelista, Andrea, additional, Moia, Riccardo, additional, Kwee, Ivo, additional, Dahl, Christina, additional, Di Rocco, Alice, additional, Stefoni, Vittorio, additional, Diop, Fary, additional, Favini, Chiara, additional, Ghione, Paola, additional, Mahmoud, Abdurraouf Mokhtar, additional, Schipani, Mattia, additional, Kolstad, Arne, additional, Barbero, Daniela, additional, Novero, Domenico, additional, Paulli, Marco, additional, Zamò, Alberto, additional, Jerkeman, Mats, additional, da Silva, Maria Gomes, additional, Santoro, Armando, additional, Molinari, Annalia, additional, Ferreri, Andres, additional, Grønbæk, Kirsten, additional, Piccin, Andrea, additional, Cortelazzo, Sergio, additional, Bertoni, Francesco, additional, Ladetto, Marco, additional, and Gaidano, Gianluca, additional

Published
2019
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27. A B-cell receptor-related gene signature predicts response to ibrutinib treatment in mantle cell lymphoma cell lines

Author

D’Agaro, Tiziana, primary, Zucchetto, Antonella, additional, Vit, Filippo, additional, Bittolo, Tamara, additional, Tissino, Erika, additional, Rossi, Francesca Maria, additional, Degan, Massimo, additional, Zaja, Francesco, additional, Bulian, Pietro, additional, Bo, Michele Dal, additional, Ferrero, Simone, additional, Ladetto, Marco, additional, Zamò, Alberto, additional, Gattei, Valter, additional, and Bomben, Riccardo, additional

Published
2019
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28. Lenalidomide Maintenance after Autologous Transplantation Prolongs PFS in Young MCL Patients: Results of the Randomized Phase III MCL 0208 Trial from Fondazione Italiana Linfomi (FIL)

Author

Ladetto, Marco, primary, Ferrero, Simone, additional, Evangelista, Andrea, additional, Mian, Michael, additional, Di Rocco, Alice, additional, Coggi, Angela, additional, Rossi, Giuseppe, additional, Re, Alessandro, additional, Stefoni, Vittorio, additional, Cavallo, Federica, additional, Chiappella, Annalisa, additional, Santoro, Armando, additional, Rusconi, Chiara, additional, Gomes da Silva, Maria, additional, Gotti, Manuel, additional, Molinari, Anna Lia, additional, Ballerini, Filippo, additional, Ferreri, Andres J M, additional, Bosi, Alberto, additional, Narni, Franco, additional, Stelitano, Caterina, additional, Zamò, Alberto, additional, Ciccone, Gianni, additional, Vitolo, Umberto, additional, Martelli, Maurizio, additional, and Cortelazzo, Sergio, additional

Published
2018
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29. Macrophages may promote cancer growth via a GM-CSF/HB-EGF paracrine loop that is enhanced by CXCL12

Author

Damiani Ernesto, Krampera Mauro, Bonifacio Massimiliano, Mauri Pierluigi, Zamò Alberto, Gottardi Michele, Rigo Antonella, Pizzolo Giovanni, and Vinante Fabrizio

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Increased numbers of tumour-associated macrophages correlate with shortened survival in some cancers. The molecular bases of this correlation are not thoroughly understood. Events triggered by CXCL12 may play a part, as CXCL12 drives the migration of both CXCR4-positive cancer cells and macrophages and may promote a molecular crosstalk between them. Results Samples of HER1-positive colon cancer metastases in liver, a tissue with high expression of CXCL12, were analysed by immunohistochemistry. In all of the patient biopsies, CD68-positive tumour-associated macrophages presented a mixed CXCL10 (M1)/CD163 (M2) pattern, expressed CXCR4, GM-CSF and HB-EGF, and some stained positive for CXCL12. Cancer cells stained positive for CXCR4, CXCL12, HER1, HER4 and GM-CSF. Regulatory interactions among these proteins were validated via experiments in vitro involving crosstalk between human mononuclear phagocytes and the cell lines DLD-1 (human colon adenocarcinoma) and HeLa (human cervical carcinoma), which express the above-mentioned ligand/receptor repertoire. CXCL12 induced mononuclear phagocytes to release HB-EGF, which activated HER1 and triggered anti-apoptotic and proliferative signals in cancer cells. The cancer cells then proliferated and released GM-CSF, which in turn activated mononuclear phagocytes and induced them to release more HB-EGF. Blockade of GM-CSF with neutralising antibodies or siRNA suppressed this loop. Conclusions CXCL12-driven stimulation of cancer cells and macrophages may elicit and reinforce a GM-CSF/HB-EGF paracrine loop, whereby macrophages contribute to cancer survival and expansion. The involvement of mixed M1/M2 GM-CSF-stimulated macrophages in a tumour-promoting loop may challenge the paradigm of tumour-favouring macrophages as polarized M2 mononuclear phagocytes.

Published
2010
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30. Analysis of colorectal cancers for human cytomegalovirus presence

Author

Menestrina Fabio, Zamò Alberto, Costantini Silvia, Bidoia Carlo, Zipeto Donato, Bender Cecilia, and Bertazzoni Umberto

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background A possible association between human cytomegalovirus (HCMV) infection and colorectal cancer progression has been inferred by the identification in tumour tissues of HCMV antigens and specific viral DNA or RNA sequences. To further investigate the relationship between HCMV and colorectal cancers we developed qualitative and quantitative PCR assay to detect HCMV DNA in 56 formalin-fixed paraffin-embedded (FFPE) tissue samples from patients belonging to 4 different histological phenotypes: adenoma; poorly, moderately and well differentiated adenocarcinomas. Results Of the 56 FFPE tested tissue samples, 6 (11%) were positive for HCMV nested PCR amplification, and more precisely 1 (5%) of 20 cases of adenoma and 5 (21%) of 24 cases of moderately differentiated adenocarcinoma. No PCR positivity was obtained in samples from well and poorly differentiated adenocarcinomas. Conclusion Our observations suggest that there is no evidence of a direct association between HCMV and colorectal cancer. Moreover, the results obtained are not supportive of a causal role of HCMV in the processes of carcinogenesis and/or progression of colorectal cancer. However, the fact that the virus may present a "hit and run" like-mechanism and HCMV can thus only be detectable at a particular stage of a processing adenocarcinoma, suggests that a significant number of colorectal cancers might have been the subject of HCMV infection that could contribute to trigger the oncogenic differentiation. Our analysis does not exclude the possibility of HCMV infection subsequent viral clearance.

Published
2009
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31. Migratory marker expression in fibroblast foci of idiopathic pulmonary fibrosis

Author

Ennas Maria, Pedron Serena, Montagna Licia, Lestani Maurizio, Reghellin Daniela, Doglioni Claudio, Zamò Alberto, Chilosi Marco, Cancellieri Alessandra, Murer Bruno, and Poletti Venerino

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Fibroblast foci (FF) are considered a relevant morphologic marker of idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), and are recognised as sites where fibrotic responses are initiated and/or perpetuated in this severe disease. Despite their relevance, the cellular and molecular mechanisms responsible for the formation of FF and their role in tissue remodelling are poorly defined. In previous studies we have provided evidence of abnormal activation of the wnt-signaling-pathway in IPF/UIP that is centred on FF and the overlying epithelium. This important morphogenetic pathway is able to trigger epithelial-mesenchymal-transition (EMT), a mechanism involved in developmental and metastatic processes, which is also potentially involved in pulmonary fibrosis. Methods Since EMT is characterised by enhancement of migratory potential of cells, we investigated the molecular profile of FF in 30 biopsies of IPF/UIP and a variety of control samples, focussing on the immunohistochemical expression of three molecules involved in cell motility and invasiveness, namely laminin-5-γ2-chain, fascin, and heat-shock-protein-27. Results We provide evidence that in UIP these three molecules are abnormally expressed in discrete clusters of bronchiolar basal cells precisely localised in FF. These cellular clusters expressed laminin-5-γ2-chain and heat-shock-protein-27 at very high levels, forming characteristic three-layered lesions defined as "sandwich-foci" (SW-FF). Upon quantitative analysis SW-FF were present in 28/30 UIP samples, representing more than 50% of recognisable FF in 21/30, but were exceedingly rare in a wide variety of lung pathologies examined as controls. In UIP, SW-FF were often observed in areas of microscopic honeycombing, and were also found at the interface between normal lung tissue and areas of dense scarring. Conclusion These molecular abnormalities strongly suggest that SW-FF represent the leading edge of pulmonary remodelling, where abnormal migration and re-epithelialisation take place, and that abnormal proliferation and migration of bronchiolar basal cells have a major role in the remodelling process characterising IPF/UIP. Further investigations will assess their possible use as reliable markers for better defining the UIP-pattern in difficult cases.

Published
2006
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32. MYC-related microRNAs signatures in non-Hodgkin B-cell lymphomas and their relationships with core cellular pathways

Author

Malpeli, Giorgio, primary, Barbi, Stefano, additional, Tosadori, Gabriele, additional, Greco, Corinna, additional, Zupo, Simonetta, additional, Pedron, Serena, additional, Brunelli, Matteo, additional, Bertolaso, Anna, additional, Scupoli, Maria Teresa, additional, Krampera, Mauro, additional, Kamga, Paul Takam, additional, Croce, Carlo Maria, additional, Calin, George Adrian, additional, Scarpa, Aldo, additional, and Zamò, Alberto, additional

Published
2018
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34. slan+ Monocytes and Macrophages Mediate CD20-Dependent B-cell Lymphoma Elimination via ADCC and ADCP

Author

Vermi, William, primary, Micheletti, Alessandra, additional, Finotti, Giulia, additional, Tecchio, Cristina, additional, Calzetti, Federica, additional, Costa, Sara, additional, Bugatti, Mattia, additional, Calza, Stefano, additional, Agostinelli, Claudio, additional, Pileri, Stefano, additional, Balzarini, Piera, additional, Tucci, Alessandra, additional, Rossi, Giuseppe, additional, Furlani, Lara, additional, Todeschini, Giuseppe, additional, Zamò, Alberto, additional, Facchetti, Fabio, additional, Lorenzi, Luisa, additional, Lonardi, Silvia, additional, and Cassatella, Marco A., additional

Published
2018
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37. A B-cell receptor-related gene signature predicts survival in mantle cell lymphoma: results from the Fondazione Italiana Linfomi MCL-0208 trial

Author

Bomben, Riccardo, primary, Ferrero, Simone, additional, D’Agaro, Tiziana, additional, Dal Bo, Michele, additional, Re, Alessandro, additional, Evangelista, Andrea, additional, Carella, Angelo Michele, additional, Zamò, Alberto, additional, Vitolo, Umberto, additional, Omedè, Paola, additional, Rusconi, Chiara, additional, Arcaini, Luca, additional, Rigacci, Luigi, additional, Luminari, Stefano, additional, Piccin, Andrea, additional, Liu, Delong, additional, Wiestner, Adrian, additional, Gaidano, Gianluca, additional, Cortelazzo, Sergio, additional, Ladetto, Marco, additional, and Gattei, Valter, additional

Published
2018
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39. Abstract PR10: FBXO11 is recurrently mutated in Burkitt lymphoma and its inactivation accelerates lymphomagenesis in Eμ-myc mice

Author

Pighi, Chiara, primary, Compagno, Mara, additional, Cheong, Taek-Chin, additional, Poggio, Teresa, additional, Wang, Qi, additional, Langellotto, Fernanda, additional, Sendamarai, Anoop, additional, Markianos, Kyriacos, additional, Celle, Paola Francia di, additional, Zamò, Alberto, additional, and Chiarle, Roberto, additional

Published
2017
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40. Multiple large osteolytic lesions in a patient with systemic mastocytosis: a challenging diagnosis

Author

Bonifacio, Massimiliano, primary, Zanotti, Roberta, additional, Guardalben, Emanuele, additional, Mimiola, Elda, additional, Scognamiglio, Francesca, additional, Perbellini, Omar, additional, De Matteis, Giovanna, additional, Escribano, Luis, additional, Bonadonna, Patrizia, additional, Grigolato, Daniela, additional, Bissoli, Sergio, additional, Parisi, Alice, additional, Zamò, Alberto, additional, Ambrosetti, Achille, additional, and Rossini, Maurizio, additional

Published
2017
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41. Pesticide toxicogenomics across scales: in vitro transcriptome predicts mechanisms and outcomes of exposure in vivo

Author

Porreca, Immacolata, primary, D’Angelo, Fulvio, additional, De Franceschi, Lucia, additional, Mattè, Alessandro, additional, Ceccarelli, Michele, additional, Iolascon, Achille, additional, Zamò, Alberto, additional, Russo, Filomena, additional, Ravo, Maria, additional, Tarallo, Roberta, additional, Scarfò, Marzia, additional, Weisz, Alessandro, additional, De Felice, Mario, additional, Mallardo, Massimo, additional, and Ambrosino, Concetta, additional

Published
2016
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42. Identification of a Novel Gene Expression Signature in Mantle Cell Lymphoma from the Fondazione Italiana Linfomi (FIL)-MCL-0208 Trial: A Focus on the B Cell Receptor Pathway

Author

Bomben, Riccardo, primary, Ferrero, Simone, additional, Dal Bo, Michele, additional, D'Agaro, Tiziana, additional, Re, Alessandro, additional, Evangelista, Andrea, additional, Carella, Angelo Michele, additional, Zamò, Alberto, additional, Vitolo, Umberto, additional, Omedè, Paola, additional, Rusconi, Chiara, additional, Arcaini, Luca, additional, Rigacci, Luigi, additional, Luminari, Stefano, additional, Cortelazzo, Sergio, additional, Ladetto, Marco, additional, and Gattei, Valter, additional

Published
2015
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44. Cellular Senescence Markers p16INK4a and p21CIP1/WAF Are Predictors of Hodgkin Lymphoma Outcome

Author

Caliò, Anna, primary, Zamò, Alberto, additional, Ponzoni, Maurilio, additional, Zanolin, Maria Elisabetta, additional, Ferreri, Andrés J.M., additional, Pedron, Serena, additional, Montagna, Licia, additional, Parolini, Claudia, additional, Fraifeld, Vadim E., additional, Wolfson, Marina, additional, Yanai, Hagai, additional, Pizzolo, Giovanni, additional, Doglioni, Claudio, additional, Vinante, Fabrizio, additional, and Chilosi, Marco, additional

Published
2015
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46. Expression and function of the TL1A/DR3 axis in chronic lymphocytic leukemia

Author

Cavallini, Chiara, primary, Lovato, Ornella, additional, Bertolaso, Anna, additional, Zoratti, Elisa, additional, Malpeli, Giorgio, additional, Mimiola, Elda, additional, Tinelli, Martina, additional, Aprili, Fiorenza, additional, Tecchio, Cristina, additional, Perbellini, Omar, additional, Scarpa, Aldo, additional, Zamò, Alberto, additional, Cassatella, Marco Antonio, additional, Pizzolo, Giovanni, additional, and Scupoli, Maria Teresa, additional

Published
2015
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47. ATM-deficiency sensitizes Mantle Cell Lymphoma cells to PARP-1 inhibitors

Author

Williamson, Chris T., Muzik, Huong, Turhan, Ali G., Zamò, Alberto, O’Connor, Mark J., Bebb, D. Gwyn, and Lees-Miller, Susan P.

Subjects
DNA Repair, Tumor Suppressor Proteins, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Lymphoma, Mantle-Cell, Trypan Blue, Poly(ADP-ribose) Polymerase Inhibitors, Protein Serine-Threonine Kinases, Article, Piperazines, DNA-Binding Proteins, Mice, Cell Line, Tumor, Radiation, Ionizing, Animals, Humans, Phthalazines, Female, Annexin A5, Phosphorylation, Neoplasm Transplantation
Abstract

Poly-ADP ribose polymerase-1 (PARP-1) inhibition is toxic to cells with mutations in the breast and ovarian cancer susceptibility genes BRCA1 or BRCA2, a concept, termed synthetic lethality. However, whether this approach is applicable to other human cancers with defects in other DNA repair genes has yet to be determined. The Ataxia-Telangiectasia Mutated (ATM) gene is altered in a number of human cancers including Mantle Cell Lymphoma (MCL). Here, we characterize a panel of MCL cell lines for ATM status and function and investigate the potential for synthetic lethality in MCL in the presence of small molecule inhibitors of PARP-1. We show that Granta-519 and UPN2 cells have low levels of ATM protein, are defective in DNA damage-induced ATM-dependent signaling, are radiation sensitive and have cell cycle checkpoint defects: all characteristics of defective ATM function. Significantly, Granta-519 and UPN2 cells were more sensitive to PARP-1 inhibition, than were the ATM-proficient MCL cell lines examined. Furthermore, the PARP-1 inhibitor olaparib (previously known as AZD2281/KU-0059436) significantly decreased tumour growth and increased overall survival in mice bearing subcutaneous xenografts of ATM-deficient Granta-519 cells, while producing only a modest effect on overall survival of mice bearing xenografts of the ATM-proficient cell line, Z138. Thus, PARP inhibitors have therapeutic potential in the treatment of MCL and the concept of synthetic lethality extends to human cancers with ATM alterations.

Published
2010

49. NOTCH1 Mutated IGHV Unmutated Chronic Lymphocytic Leukemia Cells Are Characterized By a Constitutive Overexpression of Nucleophosmin-1 and Ribosome-Associated Components

Author

Pozzo, Federico, primary, Bittolo, Tamara, additional, Tissino, Erika, additional, Rossi, Francesca Maria, additional, Bomben, Riccardo, additional, Zucchetto, Antonella, additional, Benedetti, Dania, additional, Arruga, Francesca, additional, Gizdic, Branimir, additional, Degan, Massimo, additional, Bulian, Pietro, additional, D'Arena, Giovanni, additional, Di Raimondo, Francesco, additional, Zaja, Francesco, additional, Pozzato, Gabriele, additional, Zamò, Alberto, additional, Deaglio, Silvia, additional, Rossi, Davide, additional, Gaidano, Gianluca, additional, Del Poeta, Giovanni, additional, Dal Bo, Michele, additional, and Gattei, Valter, additional

Published
2014
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50. Genome-Wide Promoter Methylation Profiling Of Splenic Marginal Zone Lymphoma (SMZL) Identifies Two Subgroups Of Patients With Distinct Genetic and Biologic Features and Different Outcomes

Author

Arribas, Alberto J., primary, Rinaldi, Andrea, additional, Kwee, Ivo, additional, Mensah, Afua A., additional, Cascione, Luciano, additional, Martinez-Climent, Jose A., additional, Oscier, David, additional, Arcaini, Luca, additional, Baldini, Luca, additional, Marasca, Roberto, additional, Thieblemont, Catherine, additional, Soulier, Jean, additional, Forconi, Francesco, additional, Zamò, Alberto, additional, Bonifacio, Massimiliano, additional, Mollejo, Manuela, additional, Facchetti, Fabio, additional, Dirnhofer, Stephan, additional, Ponzoni, Maurilio, additional, Bhagat, Govind, additional, Piris, Miguel Angel A., additional, Gaidano, Gianluca, additional, Zucca, Emanuele, additional, Rossi, Davide, additional, and Bertoni, Francesco, additional

Published
2013
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