144 results on '"Zamò, Alberto"'
Search Results
102. Application of Microfluidic Technology to the BIOMED-2 Protocol for Detection of B-Cell Clonality
- Author
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Zamò, Alberto, primary, Bertolaso, Anna, additional, van Raaij, Annemiek W.M., additional, Mancini, Francesca, additional, Scardoni, Maria, additional, Montresor, Marina, additional, Menestrina, Fabio, additional, van Krieken, Johan H.J.M., additional, Chilosi, Marco, additional, Groenen, Patricia J.T.A., additional, and Scarpa, Aldo, additional
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- 2012
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103. In Vitro and In Vivo Model of EBV-Positive Non-Hodgkin Plasmablastic Lymphoma with Focal Plasmacytic Differentiation
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Nichele, Ilaria, primary, Zamò, Alberto, additional, Bertolaso, Anna, additional, Bifari, Francesco, additional, Tinelli, Martina, additional, Franchini, Marta, additional, Stradoni, Roberta, additional, Aprili, Fiorenza, additional, Pizzolo, Giovanni, additional, and Krampera, Mauro, additional
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- 2011
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104. SNP-Arrays Provide New Insights Into the Pathogenesis of Richter Syndrome (RS)
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Rinaldi, Andrea, primary, Chigrinova, Ekaterina, additional, Kwee, Ivo, additional, Rossi, Davide, additional, Rancoita, Paola MV, additional, Strefford, Jonathan C., additional, Oscier, David Graham, additional, Stamatopoulos, Kostas, additional, Papadaki, Theodora, additional, Berger, Francoise, additional, Young, Ken H., additional, Murray, Fiona, additional, Rosenquist, Richard, additional, Greiner, Timothy C., additional, Chan, Wing C., additional, Arcaini, Luca, additional, Lucioni, Marco, additional, Marasca, Roberto, additional, Inghirami, Giorgio, additional, Ladetto, Marco, additional, Forconi, Francesco, additional, Cogliatti, Sergio, additional, Votavova, Hana, additional, Swerdlow, Steven H., additional, Stilgenbauer, Stephan, additional, Piris, Miguel, additional, Matolcsy, Andras, additional, Spagnolo, Dominic, additional, Nikitin, Eugene, additional, Zamò, Alberto, additional, Gattei, Valter, additional, Pasqualucci, Laura, additional, Zucca, Emanuele, additional, Gaidano, Gianluca, additional, and Bertoni, Francesco, additional
- Published
- 2011
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105. Improved Detection of the KIT D816V Mutation Using a Real-Time PCR Assay Allows a Finer Recognition of Patients with Indolent Systemic Mastocytosis
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Bonifacio, Massimiliano, primary, De Matteis, Giovanna, additional, De Benedittis, Caterina, additional, Perbellini, Omar, additional, Zamò, Alberto, additional, Bonadonna, Patrizia, additional, Paviati, Elisa, additional, Artuso, Anna, additional, Soverini, Simona, additional, Pizzolo, Giovanni, additional, Martinelli, Giovanni, additional, and Zanotti, Roberta, additional
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- 2011
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106. 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
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Todeschini, Giuseppe, primary, Bonifacio, Massimiliano, additional, Tecchio, Cristina, additional, Balter, Rita, additional, Carli, Giuseppe, additional, Stefani, Piero Maria, additional, Adami, Fausto, additional, Zamò, Alberto, additional, Tos, Angelo Paolo Dei, additional, Marino, Filippo, additional, Gherlinzoni, Filippo, additional, Marradi, Pierluigi, additional, Semenzato, Giampietro, additional, and Pizzolo, Giovanni, additional
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- 2011
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107. Primary role of multiparametric flow cytometry in the diagnostic work-up of indolent clonal mast cell disorders
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Perbellini, Omar, primary, Zamò, Alberto, additional, Colarossi, Sabrina, additional, Zampieri, Francesca, additional, Zoppi, Francesca, additional, Bonadonna, Patrizia, additional, Schena, Donatella, additional, Artuso, Anna, additional, Martinelli, Giovanni, additional, Chilosi, Marco, additional, Pizzolo, Giovanni, additional, and Zanotti, Roberta, additional
- Published
- 2011
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108. Proteomics of human cancer tissues and cells
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Cecconi, Daniela, primary and Zamò, Alberto, additional
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- 2011
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109. Haploidentical hematopoietic stem cell transplantation in a myelofibrosis patient with primary graft failure.
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Tecchio, Cristina, Andreini, Angelo, Costantini, Claudio, Zamò, Alberto, de Sabata, Donata, Aprili, Fiorenza, Galavotti, Roberta, Guardalben, Emanuele, and Benedetti, Fabio
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MYELOFIBROSIS ,HEMATOPOIETIC stem cell transplantation ,GRAFT rejection ,THERAPEUTICS - Abstract
The prognosis of patients affected by myelofibrosis (MF) is usually dismal and allogeneic hematopoietic stem cell transplantation (HSCT) remains the only cure. The number of HSCTs in MF patients has recently increased. However, a major obstacle is still represented by primary graft failure (PGF). Currently there are no definitive guidelines for the treatment of PGF and a second HSCT can be performed only when an allogeneic donor is rapidly available. Herein we report on a MF patient with PGF after an unrelated HSCT, who was rescued by a non-myeloablative, unmanipulated, haploidentical HSCT that resulted in persistent engraftment and bone-marrow fibrosis regression, but not in a long-term disease control. Based on this experience we briefly review the role of different conditioning regimens and hematopoietic stem cell sources in the setting of HSCT for MF patients with PGF. The role of haploidentical donors in MF patients lacking HLAmatched relatives is also discussed. [ABSTRACT FROM AUTHOR]
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- 2017
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110. Macrophages may promote cancer growth via a GM-CSF/HB-EGF paracrine loop that is enhanced by CXCL12
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Rigo, Antonella, primary, Gottardi, Michele, additional, Zamò, Alberto, additional, Mauri, Pierluigi, additional, Bonifacio, Massimiliano, additional, Krampera, Mauro, additional, Damiani, Ernesto, additional, Pizzolo, Giovanni, additional, and Vinante, Fabrizio, additional
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- 2010
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111. Gene Expression Profiling Uncovers Molecular Classifiers for the Recognition of Anaplastic Large-Cell Lymphoma Within Peripheral T-Cell Neoplasms
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Piva, Roberto, primary, Agnelli, Luca, additional, Pellegrino, Elisa, additional, Todoerti, Katia, additional, Grosso, Valentina, additional, Tamagno, Ilaria, additional, Fornari, Alessandro, additional, Martinoglio, Barbara, additional, Medico, Enzo, additional, Zamò, Alberto, additional, Facchetti, Fabio, additional, Ponzoni, Maurilio, additional, Geissinger, Eva, additional, Rosenwald, Andreas, additional, Müller-Hermelink, Hans Konrad, additional, De Wolf-Peeters, Christiane, additional, Piccaluga, Pier Paolo, additional, Pileri, Stefano, additional, Neri, Antonino, additional, and Inghirami, Giorgio, additional
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- 2010
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112. ATM Deficiency Sensitizes Mantle Cell Lymphoma Cells to Poly(ADP-Ribose) Polymerase-1 Inhibitors
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Williamson, Chris T., primary, Muzik, Huong, additional, Turhan, Ali G., additional, Zamò, Alberto, additional, O'Connor, Mark J., additional, Bebb, D. Gwyn, additional, and Lees-Miller, Susan P., additional
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- 2010
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113. Analysis of colorectal cancers for human cytomegalovirus presence
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Bender, Cecilia, primary, Zipeto, Donato, additional, Bidoia, Carlo, additional, Costantini, Silvia, additional, Zamò, Alberto, additional, Menestrina, Fabio, additional, and Bertazzoni, Umberto, additional
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- 2009
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114. Signal transduction pathways of mantle cell lymphoma: A phosphoproteome‐based study
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Cecconi, Daniela, primary, Zamò, Alberto, additional, Bianchi, Elena, additional, Parisi, Alice, additional, Barbi, Stefano, additional, Milli, Alberto, additional, Rinalducci, Sara, additional, Rosenwald, Andreas, additional, Hartmann, Elena, additional, Zolla, Lello, additional, and Chilosi, Marco, additional
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- 2008
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115. Induction of Apoptosis in Jeko-1 Mantle Cell Lymphoma Cell Line by Resveratrol: A Proteomic Analysis
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Cecconi, Daniela, primary, Zamò, Alberto, additional, Parisi, Alice, additional, Bianchi, Elena, additional, Parolini, Claudia, additional, Timperio, Anna Maria, additional, Zolla, Lello, additional, and Chilosi, Marco, additional
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- 2008
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116. Migratory marker expression in fibroblast foci of idiopathic pulmonary fibrosis
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Chilosi, Marco, primary, Zamò, Alberto, additional, Doglioni, Claudio, additional, Reghellin, Daniela, additional, Lestani, Maurizio, additional, Montagna, Licia, additional, Pedron, Serena, additional, Ennas, Maria Grazia, additional, Cancellieri, Alessandra, additional, Murer, Bruno, additional, and Poletti, Venerino, additional
- Published
- 2006
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117. Multivariate statistical tools applied to the characterization of the proteomic profiles of two human lymphoma cell lines by two‐dimensional gel electrophoresis
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Marengo, Emilio, primary, Robotti, Elisa, additional, Bobba, Marco, additional, Liparota, Maria Cristina, additional, Rustichelli, Chiara, additional, Zamò, Alberto, additional, Chilosi, Marco, additional, and Righetti, Pier Giorgio, additional
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- 2006
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118. Aberrant Wnt/β-Catenin Pathway Activation in Idiopathic Pulmonary Fibrosis
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Chilosi, Marco, primary, Poletti, Venerino, additional, Zamò, Alberto, additional, Lestani, Maurizio, additional, Montagna, Licia, additional, Piccoli, Paola, additional, Pedron, Serena, additional, Bertaso, Manuela, additional, Scarpa, Aldo, additional, Murer, Bruno, additional, Cancellieri, Alessandra, additional, Maestro, Roberta, additional, Semenzato, Gianpietro, additional, and Doglioni, Claudio, additional
- Published
- 2003
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119. Role of disease‐causing genes in sporadic pancreatic endocrine tumors: MEN1 andVHL
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Moore, Patrick S., primary, Missiaglia, Edoardo, additional, Antonello, Davide, additional, Zamò, Alberto, additional, Zamboni, Giuseppe, additional, Corleto, Vito, additional, Falconi, Massimo, additional, and Scarpa, Aldo, additional
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- 2001
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120. Constitutive expression of DeltaN-p63alpha isoform in human thymus and thymic epithelial tumours.
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Chilosi, Marco, Zamò, Alberto, Brighenti, Antonietta, Malpeli, Giorgio, Montagna, Licia, Piccoli, Paola, Pedron, Serena, Lestani, Maurizio, Inghirami, Giorgio, Scarpa, Aldo, Doglioni, Claudio, and Menestrina, Fabio
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PROTEIN metabolism ,RNA metabolism ,RNA analysis ,CELL nuclei ,COMPARATIVE studies ,FLUORESCENT antibody technique ,RESEARCH methodology ,MEDIASTINAL tumors ,MEDICAL cooperation ,POLYMERASE chain reaction ,PROTEINS ,RESEARCH ,THYMUS ,THYMUS tumors ,DNA-binding proteins ,EVALUATION research ,REVERSE transcriptase polymerase chain reaction - Abstract
p63, a member of the p53 family, is involved in the survival and differentiation of reserve/stem cells in different epithelia. To unveil the possible role of p63 in thymic physiology and pathology, we investigated the expression of p63 isoforms in normal thymus, thymomas and other mediastinal tumours. All samples were analysed using immunohistochemistry with three different antibodies: 4A4 antibody recognising all p63 isoforms, p40 antibody reacting only with truncated dominant-negative isoforms (DeltaN-p63) and H-129 antibody recognising all alpha-isoforms. Reverse-transcription polymerase chain reaction (RT-PCR), and real-time PCR analyses were performed on RNA extracted from frozen samples of four thymomas and two primary-mediastinal large-B-cell lymphoma (PMLBCL). In normal thymus, DeltaN-p63alpha was expressed in all cortical and medullary epithelial cells, with decreasing intensity in Hassall's corpuscles. This phenotype was conserved in neoplastic transformation since all 54 investigated thymomas (World Health Organization types A, AB, B1, B2, B3, C) expressed DeltaN-p63alpha (virtually 100% cells). The predominance of DeltaN-p63alpha isoform mRNA was confirmed by real-time PCR. Among other mediastinal tumours, DeltaN-p63alpha was only expressed in those displaying either a stratified epithelial component (teratomas) or epidermoid differentiation (lung carcinoma). Among lymphomas, T-cell-precursor lymphomas did not express p63, whereas most PMLBCL expressed TA-p63alpha (7/8). [ABSTRACT FROM AUTHOR]
- Published
- 2003
121. VDJSeq-Solver: In Silico V(D)J Recombination Detection Tool
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Paciello, Giulia, Acquaviva, Andrea, Pighi, Chiara, Ferrarini, Alberto, Macii, Enrico, Zamo’, Alberto, and Ficarra, Elisa
- Abstract
In this paper we present VDJSeq-Solver, a methodology and tool to identify clonal lymphocyte populations from paired-end RNA Sequencing reads derived from the sequencing of mRNA neoplastic cells. The tool detects the main clone that characterises the tissue of interest by recognizing the most abundant V(D)J rearrangement among the existing ones in the sample under study. The exact sequence of the clone identified is capable of accounting for the modifications introduced by the enzymatic processes. The proposed tool overcomes limitations of currently available lymphocyte rearrangements recognition methods, working on a single sequence at a time, that are not applicable to high-throughput sequencing data. In this work, VDJSeq-Solver has been applied to correctly detect the main clone and identify its sequence on five Mantle Cell Lymphoma samples; then the tool has been tested on twelve Diffuse Large B-Cell Lymphoma samples. In order to comply with the privacy, ethics and intellectual property policies of the University Hospital and the University of Verona, data is available upon request to supporto.utenti@ateneo.univr.it after signing a mandatory Materials Transfer Agreement. VDJSeq-Solver JAVA/Perl/Bash software implementation is free and available at http://eda.polito.it/VDJSeq-Solver/.
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- 2015
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122. Microfluidic Deletion/Insertion Analysis for Rapid Screening of KITand PDGFRAMutations in CD117-Positive Gastrointestinal Stromal Tumors
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Zamò, Alberto, Bertolaso, Anna, Franceschetti, Ilaria, Weirich, Gregor, Capelli, Paola, Pecori, Sara, Chilosi, Marco, Hoefler, Heinz, Menestrina, Fabio, and Scarpa, Aldo
- Abstract
Gastrointestinal stromal tumors (GISTs) frequently harbor mutations in the KITand PDGFRAgenes, the presence and type of which correlate with the response to the kinase inhibitor imatinib mesylate. Because most GIST mutations are deletions/insertions, we used a microfluidic apparatus to detect these size variations in polymerase chain reaction-amplified DNA. This approach, termed microfluidic deletion/insertion analysis (MIDIA), identified mutations in 30 of 50 DNA samples from paraffin-embedded CD117-positive GISTs (60%), comprising 25 deletions and five insertions. Sequencing of 14 MIDIA-positive samples confirmed the deletions/insertions, including two 3-bp alterations. Sequencing of all 20 MIDIA-negative samples also showed highly consistent results with MIDIA because 10 cases were wild type and eight displayed a single base substitution in which detection by MIDIA was not expected. Sequencing also revealed a 3-bp deletion undetected by MIDIA, thus establishing the resolution limit of MIDIA at deletions/insertions ≥3 bp. Denaturing high-pressure liquid chromatography analysis confirmed all mutations detected by MIDIA and sequencing. We pro-pose MIDIA as the first step in mutational screening of GIST because it allowed the detection of 75% of mutated cases (94% of deletions/insertions) in less than 30 minutes after polymerase chain reaction amplification and at a lower cost compared with denaturing high-pressure liquid chromatography and sequencing, which might then be used only for MIDIA-negative cases.
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- 2007
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123. Frequent mutations of FBXO11 highlight BCL6 as a therapeutic target in Burkitt lymphoma
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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, di Celle, Paola Francia, Whitfield, Jonathan R., Soucek, Laura, Voena, Claudia, Calogero, Raffaele, Morin, Ryan D., Staudt, Louis M., Siebert, Reiner, Zamò, Alberto, and Chiarle, Roberto
- Abstract
The expression of BCL6 in B cell lymphoma can be deregulated by chromosomal translocations, somatic mutations in the promoter regulatory regions or reduced proteasome-mediated degradation. FBXO11 was recently identified as a ubiquitin ligase involved in the degradation of BCL6 and is frequently inactivated in lymphoma or other tumors. Here, we show that FBXO11mutations are found in 23% of Burkitt lymphoma (BL) patients. FBXO11mutations impaired BCL6 degradation and the deletion of FBXO11 protein completely stabilized BCL6 levels in human BL cell lines. Conditional deletion of either one or two copies of the FBXO11gene in mice cooperated with oncogenic MYC and accelerated B cell lymphoma onset, providing experimental evidence that FBXO11 is a haplo-insufficient oncosuppressor in B cell lymphoma. In WT and FBXO11-deficient BL mouse and human cell lines, targeting BCL6 via specific degrader or inhibitors partially impaired lymphoma growth in vitroand in vivo. Inhibition of MYC by the Omomyc mini-protein blocked cell proliferation and increased apoptosis, effects further increased by combined BCL6 targeting. Thus, by validating the functional role of FBXO11mutations in BL we further highlight the key role of BCL6 in BL biology and provide evidence that innovative therapeutic approaches such as BCL6 degraders and direct MYC inhibition could be exploited as a targeted therapy for BL.
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- 2021
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124. Delphi, a Data Warehouse to Discover Associations between Variables in Clinical Trials: Application to the Fondazione Italiana Linfomi (FIL) MCL0208 Phase III Trial
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Zaccaria, Gian Maria, Ferrero, Simone, Evangelista, Andrea, Rosati, Samanta, Castagneri, Cristina, Ghislieri, Marco, Daniela, Barbero, Genuardi, Elisa, Lo Schirico, Mariella, Zamò, Alberto, Vitolo, Umberto, Bomben, Riccardo, Gattei, Valter, Galimberti, Sara, Di Paolo, Antonello, Rossi, Davide, Gaidano, Gianluca, Di Rocco, Alice, Cortelazzo, Sergio, Boccadoro, Mario, Balestra, Gabriella, and Ladetto, Marco
- Abstract
Background and aims.Data collection in clinical trials is becoming complex, with huge amount of clinical and biological variables that need to be recorded, verified and analyzed to confirm obvious and identify unexpected associations. Outside the medical field, data warehouses (DWs) are widely employed to achieve these objectives. To verify whether DWs might be useful for data quality and association analysis, a team of clinicians, biologists, statisticians and biomedical engineers developed DELPHI (“Data ELaboration to Predict Hypothetical assocIations”). The tool has been suited to a large clinical trial from the Fondazione Italiana Linfomi (FIL), including all the clinical, biological and mutational features collected both in the trial and in the ancillary studies. Herein we present the first results, related to baseline variables: 1) creation of a broad DW (including 350 variables for 300 patients, thus > 105data); 2) data harmonization and quality control; 3) discovery of unexpected associations and (in a later phase) outcome correlations; 4) results visualization.
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- 2017
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125. NOTCH1Mutated IGHVUnmutated Chronic Lymphocytic Leukemia Cells Are Characterized By a Constitutive Overexpression of Nucleophosmin-1 and Ribosome-Associated Components
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Pozzo, Federico, Bittolo, Tamara, Tissino, Erika, Rossi, Francesca Maria, Bomben, Riccardo, Zucchetto, Antonella, Benedetti, Dania, Arruga, Francesca, Gizdic, Branimir, Degan, Massimo, Bulian, Pietro, D’Arena, Giovanni, Di Raimondo, Francesco, Zaja, Francesco, Pozzato, Gabriele, Zamò, Alberto, Deaglio, Silvia, Rossi, Davide, Gaidano, Gianluca, Del Poeta, Giovanni, Dal Bo, Michele, and Gattei, Valter
- Abstract
Background:stabilizing mutations of NOTCH1have been identified in about 10% of chronic lymphocytic leukemia (CLL) cases at diagnosis, with a higher frequency in unmutated IGHV(IGHV-UM), immuno-chemorefractory or advanced disease phase CLL, and have been associated with particularly unfavourable prognosis (Rossi et al, Blood, 2012; Del Poeta et al, Br J Haematol, 2013; Stingelbauer et al, Blood, 2014). In CLL, all NOTCH1mutations disrupt the C-terminal PEST domain (about 80% of which are a 7544-7545delCT frameshift deletion) and cause an accumulation of an active NOTCH1 isoform.
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- 2014
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126. Nucleophosmin-1 and Ribosome-Associated Components Are Constitutively Overexpressed in NOTCH1Mutated IGHVUnmutated CLL
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Dal Bo, Michele, Pozzo, Federico, Bomben, Riccardo, Zucchetto, Antonella, Tissino, Erika, Benedetti, Dania, Degan, Massimo, Rossi, Francesca Maria, Bulian, Pietro, D'Agaro, Tiziana, Dereani, Sara, Rossi, Davide, Zamò, Alberto, Zaja, Francesco, Pozzato, Gabriele, Di Raimondo, Francesco, Gaidano, Gianluca, Del Poeta, Giovanni, and Gattei, Valter
- Abstract
Abstract 3880
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- 2012
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127. CAL2 monoclonal antibody is a rapid and sensitive assay for the detection of calreticulin mutations in essential thrombocythemia patients.
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Bonifacio, Massimiliano, Montemezzi, Rachele, Parisi, Alice, De Matteis, Giovanna, Bertorelle, Roberta, Scaffidi, Luigi, Candiotto, Cinzia, Lippi, Giuseppe, Zamò, Alberto, Chilosi, Marco, Pizzolo, Giovanni, Scarpa, Aldo, and Krampera, Mauro
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MONOCLONAL antibodies , *BONE marrow , *FRAMESHIFT mutation , *CALRETICULIN , *MEGAKARYOCYTES , *CELL metabolism , *PROTEIN metabolism , *BIOPSY , *CALCIUM-binding proteins , *CELLS , *CLINICAL trials , *COMPARATIVE studies , *IMMUNITY , *IMMUNOHISTOCHEMISTRY , *RESEARCH methodology , *MEDICAL cooperation , *GENETIC mutation , *PROTEINS , *RESEARCH , *THROMBOCYTOSIS , *EVALUATION research , *RETROSPECTIVE studies - Abstract
Calreticulin (CALR) mutations are detected in the majority of JAK2 wild type patients with essential thrombocythemia (ET). Unlike JAK2V617F and MPL point mutations, CALR mutations are highly heterogeneous, with several types of indels being reported so far. CAL2 is a monoclonal antibody specifically recognizing the C-neoterminal peptide derived from all the frameshift mutations of CALR. We retrospectively analysed 172 ET patients diagnosed at our Institution from 1980 to 2015. In JAK2V617F- and MPLW515K/L-wild type patients CALR mutations were searched on peripheral blood and CAL2 immunostaining was performed on bone marrow. In addition, bone marrow biopsies were histologically reviewed for megakaryocytic features. Thirty-one patients (18%) were CALR-mutated. Concordance between molecular and immunohistological detection of CALR mutations was near complete, albeit a single patient was found to be positive by molecular tests only. Two patterns were defined in CAL2-positive bone marrow samples, characterized by staining of almost only megakaryocytes (pattern A: 41%) or staining of megakaryocytes and ≥ 2% small non megakaryocytic elements (pattern B: 59%), at least partially being myeloid precursors. Pattern B biopsies had higher cellularity and number of megakaryocytes compared to pattern A samples. In this series, CAL2 allowed rapid and cost-efficient identification of CALR-mutated ET patients. The biological significance of different staining pattern should be confirmed in wider and independent series. [ABSTRACT FROM AUTHOR]
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- 2019
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128. The histological and molecular spectrum of lipoblastoma: A case series with identification of three novel gene fusions by targeted RNA-sequencing.
- Author
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Gerhard-Hartmann, Elena, Vokuhl, Christian, Roth, Sabine, Steinmüller, Tabea, Rosenfeldt, Mathias, Zamò, Alberto, Rosenwald, Andreas, Appenzeller, Silke, Ernestus, Karen, and Maurus, Katja
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GENE fusion , *LIPOSARCOMA , *MOLECULAR spectra , *RNA sequencing , *BENIGN tumors , *CHILD patients - Abstract
Lipoblastoma is a rare benign mesenchymal neoplasm that typically occurs in infancy but may also occur in older age groups and various locations. Thus, there are often numerous clinical differential diagnoses. Moreover, lipoblastomas can show a broad histologic spectrum, which can hamper the correct diagnosis, particularly in small biopsies. At the genomic level, lipoblastomas are characterized by chromosomal fusions involving the PLAG1 gene. We investigated 11 lipoblastoma samples from 10 pediatric patients (age range five months to 12 years), including one patient with local recurrence, in view of their histopathological features, and performed targeted RNA sequencing. We found a broad histological spectrum with some tumors with prominent myxoid changes, but also tumors composed mainly of mature adipocytic cells, and classified the cases according to the literature as classic (mixed), maturing, or myxoid subtype. By targeted RNA sequencing analysis, we identified characteristic PLAG1 rearrangements in 70% of the investigated cases. Moreover, these analyses revealed three novel gene fusions, two affecting the PLAG1 gene and one involving HMGA2. Besides, we performed PLAG1 immunohistochemistry and identified positive cells, typically immature adipocytic cells and spindle cells, at various numbers in all cases. However, in the maturing areas, only very sparsely positive cells were found, limiting the value of the PLAG1 immunohistochemistry as an adjunct in the diagnosis of lipoblastoma, particularly for the maturing subtype and small biopsies. The presented case series confirms the broad morphological spectrum of lipoblastoma described in the literature and underlines the value of modern molecular diagnostic approaches as a supportive diagnostic tool in challenging cases and for gaining further insights into the molecular basis of this rare mesenchymal tumor. [ABSTRACT FROM AUTHOR]
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- 2021
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129. Pesticide toxicogenomics across scales: in vitro transcriptome predicts mechanisms and outcomes of exposure in vivo
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Lucia De Franceschi, Fulvio D'Angelo, Alessandro Weisz, Concetta Ambrosino, Achille Iolascon, Immacolata Porreca, Roberta Tarallo, Michele Ceccarelli, Maria Ravo, Massimo Mallardo, Marzia Scarfò, Mario De Felice, Alessandro Matte, Filomena Russo, Alberto Zamò, Porreca, Immacolata, D'Angelo, Fulvio, De Franceschi, Lucia, Mattè, Alessandro, Ceccarelli, Michele, Iolascon, Achille, Zamò, Alberto, Russo, Filomena, Ravo, Maria, Tarallo, Roberta, Scarfò, Marzia, Weisz, Alessandro, DE FELICE, Mario, Mallardo, Massimo, and Ambrosino, Concetta
- Subjects
0301 basic medicine ,Male ,Thyroid Gland ,Ethylenethiourea ,Biology ,Bioinformatics ,Article ,Transcriptome ,03 medical and health sciences ,Mice ,In vivo ,Toxicity Tests ,Animals ,Humans ,Pesticides ,toxicogenomics ,Gene ,Cells, Cultured ,Multidisciplinary ,Gene Expression Profiling ,In vitro ,Cell biology ,Hematopoiesis ,Rats ,Pesticide ,Gene expression profiling ,Haematopoiesis ,030104 developmental biology ,Toxicity ,Female ,In vitro Omics analysis (i.e. transcriptome) ,Chlorpyrifos ,Toxicogenomics - Abstract
In vitro Omics analysis (i.e. transcriptome) is suggested to predict in vivo toxicity and adverse effects in humans, although the causal link between high-throughput data and effects in vivo is not easily established. Indeed, the chemical-organism interaction can involve processes, such as adaptation, not established in cell cultures. Starting from this consideration we investigate the transcriptomic response of immortalized thyrocytes to ethylenthiourea and chlorpyrifos. In vitro data revealed specific and common genes/mechanisms of toxicity, controlling the proliferation/survival of the thyrocytes and unrelated hematopoietic cell lineages. These results were phenotypically confirmed in vivo by the reduction of circulating T4 hormone and the development of pancytopenia after long exposure. Our data imply that in vitro toxicogenomics is a powerful tool in predicting adverse effects in vivo, experimentally confirming the vision described as Tox21c (Toxicity Testing in the 21st century) although not fully recapitulating the biocomplexity of a living animal.
- Published
- 2016
130. The impact of sensitive KIT D816V detection on recognition of Indolent Systemic Mastocytosis
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Fiorenza Aprili, Elisa Paviati, Alberto Zamò, Giovanni Pizzolo, Giovanna De Matteis, Massimiliano Bonifacio, Giuseppe Carli, Marta Sartori, Andrés C. García-Montero, Gian Cesare Guidi, Giovanni Martinelli, Simona Soverini, Roberta Zanotti, Omar Perbellini, Caterina De Benedittis, Patrizia Bonadonna, Beatrice Caruso, Sabrina Colarossi, De Matteis, Giovanna, Zanotti, Roberta, Colarossi, Sabrina, De Benedittis, Caterina, Garcia-Montero, Andrè, Bonifacio, Massimiliano, Sartori, Marta, Aprili, Fiorenza, Caruso, Beatrice, Paviati, Elisa, Carli, Giuseppe, Perbellini, Omar, Zamò, Alberto, Bonadonna, Patrizia, Pizzolo, Giovanni, Guidi, Giancesare, Martinelli, Giovanni, and Soverini, Simona
- Subjects
Male ,Cancer Research ,Pathology ,D-HPLC ,Bone Marrow ,Cytology ,Outpatient clinic ,Sequencing ,Systemic mastocytosis ,Chromatography, High Pressure Liquid ,Aged, 80 and over ,Sanger sequencing ,Reverse Transcriptase Polymerase Chain Reaction ,Medicine (all) ,KIT ,Hematology ,Middle Aged ,Prognosis ,Proto-Oncogene Proteins c-kit ,Real-time polymerase chain reaction ,D816V ,Oncology ,Monoclonal ,symbols ,Female ,Real time PCR ,Restriction fragment length polymorphism ,Polymorphism, Restriction Fragment Length ,Human ,Adult ,medicine.medical_specialty ,Prognosi ,Real-Time Polymerase Chain Reaction ,Follow-Up Studie ,Young Adult ,symbols.namesake ,Mastocytosis, Systemic ,Biomarkers, Tumor ,medicine ,Humans ,Point Mutation ,RNA, Messenger ,Aged ,Cutaneous Mastocytosis ,business.industry ,medicine.disease ,Systemic mastocytosi ,business ,Follow-Up Studies - Abstract
Patients with Systemic Mastocytosis (SM) need a highly sensitive diagnostic test for D816V detection of the KIT receptor gene.Along with histology/cytology and flow cytometry evaluation, bone marrow (BM) from 110 consecutive adult patients referred with a suspicion of SM to Multidisciplinary Outpatient Clinic for Mastocytosis in Verona were tested both by Amplification Refractory Mutation System Reverse Transcriptase quantitative real time Polymerase Chain Reaction (ARMS-RT-qPCR) and RT-PCR. +. Restriction Fragment Length Polymorphism (RFLP) followed by Denaturing-High Performance Liquid Chromatography (D-HPLC) and Sanger sequencing.ARMS-RT-qPCR identified D816V mutation in 77 patients, corresponding to 100% of cases showing CD25+ mast cells (MCs) whereas RT-PCR+RFLP/D-HPLC+sequencing revealed D816V mutations in 47 patients.According to the 2008 WHO criteria 75 SM, 1 Cutaneous Mastocytosis (CM), 1 monoclonal MC activation syndrome (MMAS), and 1 SM Associated with Haematologic Non-Mast Cell Disorder (SM-AHNMD) were diagnosed. Seventeen out 75 SM patients (23%) would have not satisfied sufficient WHO criteria on the basis of the sole RT-PCR+RFLP: these patients had significantly lower serum tryptase levels and amount of CD25+ MCs.Therefore, ARMS-RT-qPCR might result particularly useful, in patients that do not fulfil major BM histological criterion, for the recognition of indolent SM with a very low MC burden.
- Published
- 2015
131. DNA methylation-profiling identifies two splenic marginal zone lymphoma subgroups with different clinical and genetic features
- Author
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Alberto Zamò, Afua Adjeiwaa Mensah, Alberto J. Arribas, Govind Bhagat, Emanuele Zucca, Jose A. Martinez-Climent, Luciano Cascione, Miguel A. Piris, Maurilio Ponzoni, Gianluca Gaidano, Francesco Forconi, Francesco Bertoni, Manuela Mollejo, Fabio Facchetti, Davide Rossi, Ivo Kwee, Roberto Marasca, Eloy F. Robles, David Oscier, Luca Baldini, Luca Arcaini, Catherine Thieblemont, Massimiliano Bonifacio, Andrea Rinaldi, Josette Brière, Stephan Dirnhofer, 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
- Subjects
Male ,Lymphoma ,DNA Mutational Analysis ,Marginal Zone ,Kaplan-Meier Estimate ,Cell Transformation ,Biochemistry ,chemistry.chemical_compound ,80 and over ,Cluster Analysis ,Promoter Regions, Genetic ,Splenic marginal zone lymphoma ,Epigenomics ,Aged, 80 and over ,Methylation ,Hematology ,Middle Aged ,Prognosis ,Phenotype ,Immunology ,Cell Biology ,Cell Transformation, Neoplastic ,Treatment Outcome ,DNA methylation ,Female ,Splenic Marginal Zone Lymphoma ,Adult ,promoter methylation ,Biology ,Promoter Regions ,Kruppel-Like Factor 4 ,Genetic ,medicine ,Humans ,Epigenetics ,Aged ,Cell Proliferation ,Gene Expression Profiling ,Lymphoma, B-Cell, Marginal Zone ,Mutation ,Splenic Neoplasms ,DNA Methylation ,Neoplastic ,B-Cell ,medicine.disease ,Demethylating agent ,Gene expression profiling ,chemistry ,Splenic Marginal Zone Lymphoma, DNA methylation ,Cancer research - Abstract
Splenic marginal zone lymphoma is a rare lymphoma. Loss of 7q31 and somatic mutations affecting the NOTCH2 and KLF2 genes are the commonest genomic aberrations. Epigenetic changes can be pharmacologically reverted; therefore, identification of groups of patients with specific epigenomic alterations might have therapeutic relevance. Here we integrated genome-wide DNA-promoter methylation profiling with gene expression profiling, and clinical and biological variables. An unsupervised clustering analysis of a test series of 98 samples identified 2 clusters with different degrees of promoter methylation. The cluster comprising samples with higher-promoter methylation (High-M) had a poorer overall survival compared with the lower (Low-M) cluster. The prognostic relevance of the High-M phenotype was confirmed in an independent validation set of 36 patients. In the whole series, the High-M phenotype was associated with IGHV1-02 usage, mutations of NOTCH2 gene, 7q31-32 loss, and histologic transformation. In the High-M set, a number of tumor-suppressor genes were methylated and repressed. PRC2 subunit genes and several prosurvival lymphoma genes were unmethylated and overexpressed. A model based on the methylation of 3 genes (CACNB2, HTRA1, KLF4) identified a poorer-outcome patient subset. Exposure of splenic marginal zone lymphoma cell lines to a demethylating agent caused partial reversion of the High-M phenotype and inhibition of proliferation.
- Published
- 2015
132. The many faces of nodal and splenic marginal zone lymphomas. A report of the 2022 EA4HP/SH lymphoma workshop.
- Author
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Zamò A, van den Brand M, Climent F, de Leval L, Dirnhofer S, Leoncini L, Ng SB, Ondrejka SL, Quintanilla-Martinez L, Soma L, and Wotherspoon A
- Subjects
- Humans, Child, Spleen pathology, Bone Marrow pathology, Hyperplasia pathology, Lymphoma, B-Cell, Marginal Zone genetics, Lymphoma, Follicular pathology, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Splenic Neoplasms pathology
- Abstract
Session 3 of the lymphoma workshop of the XXI joint meeting of the European Association for Haematopathology and the Society for Hematopathology took place in Florence, Italy, on September 22, 2022. The topics of this session were splenic and nodal marginal zone lymphomas, transformation in marginal zone lymphomas, and pediatric nodal marginal zone lymphomas and their differential diagnosis as well as related entities. Forty-two cases in these categories were submitted to the workshop, including splenic lymphomas (marginal zone and diffuse red pulp lymphomas), transformed marginal zone lymphomas (splenic and nodal), nodal marginal zone lymphomas with increased TFH-cells, and pediatric nodal marginal zone lymphomas. The case review highlighted some of the principal problems in the diagnosis of marginal zone lymphomas, including the difficulties in the distinction between splenic marginal zone lymphoma, splenic diffuse red pulp lymphoma, and hairy cell leukemia variant/splenic B-cell lymphoma with prominent nucleoli which requires integration of clinical features, immunophenotype, and morphology in blood, bone marrow, and spleen; cases of marginal zone lymphoma with markedly increased TFH-cells, simulating a T-cell lymphoma, where molecular studies (clonality and mutation detection) can help to establish the final diagnosis; the criteria for transformation of marginal zone lymphomas, which are still unclear and might require the integration of morphological and molecular data; the concept of an overlapping spectrum between pediatric nodal marginal zone lymphoma and pediatric-type follicular lymphoma; and the distinction between pediatric nodal marginal zone lymphoma and "atypical" marginal zone hyperplasia, where molecular studies are mandatory to correctly classify cases., (© 2023. The Author(s).)
- Published
- 2023
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133. Correction to: Cavity-based lymphomas: challenges and novel concepts. A report of the 2022 EA4HP/SH lymphoma workshop.
- Author
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Di Napoli A, Soma L, Quintanilla-Martinez L, de Leval L, Leoncini L, Zamò A, Ng SB, Ondrejka SL, Climent F, Wotherspoon A, and Dirnhofer S
- Published
- 2023
- Full Text
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134. Cavity-based lymphomas: challenges and novel concepts. A report of the 2022 EA4HP/SH lymphoma workshop.
- Author
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Di Napoli A, Soma L, Quintanilla-Martinez L, de Leval L, Leoncini L, Zamò A, Ng SB, Ondrejka SL, Climent F, Wotherspoon A, and Dirnhofer S
- Subjects
- Humans, Lymphoma, Primary Effusion pathology, Herpesvirus 8, Human, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Large-Cell, Anaplastic, Lymphoproliferative Disorders
- Abstract
The 2022 European Association for Haematopathology/Society for Hematopathology lymphoma workshop session on cavity-based lymphomas included sixty-eight cases in seven sections. The disease entities discussed include primary effusion lymphomas (PEL), extracavitary primary effusion lymphomas and confounding entities (ECPEL), HHV8-negative B-lineage lymphomas-effusion based (EBV-negative, EBV-positive, and plasmablastic types), diffuse large B-cell lymphoma associated with chronic inflammation, fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL), breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), and other lymphomas presenting as an effusion. All entities above are discussed; however, three are delved into greater detail given the challenges with classification: ECPEL, HHV8-negative effusion-based lymphomas, and FA-DLBCL. Cases exemplifying the diagnostic difficulty in differentiating ECPEL from HHV8-positive diffuse large B-cell lymphoma and germinotropic lymphoproliferative disorder were discussed. The more recently recognized effusion-based HHV8-negative large B-cell lymphoma is explored, with several cases submitted raising the question if this subset should be carved out as a specific entity, and if so, what should be the refining diagnostic criteria. Case submissions to the FA-DLBCL section yielded one of the largest case series to date, including classic cases, cases furthering the discussion on disease sites and prognosis, as well as novel concepts to be considered in this entity. The 2022 EA4HP/SH workshop cases allowed for further confirmation of the characteristics of some of the more historically accepted cavity-based lymphomas, as well as further inquiry and debate on relatively new or evolving entities., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
135. Correction to: The many faces of nodal and splenic marginal zone lymphomas. A report of the 2022 EA4HP/SH lymphoma workshop.
- Author
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Zamò A, van den Brand M, Climent F, de Leval L, Dirnhofer S, Leoncini L, Ng SB, Ondrejka SL, Quintanilla-Martinez L, Soma L, and Wotherspoon A
- Published
- 2023
- Full Text
- View/download PDF
136. [Classification of indolent B-cell lymphomas : Novelties and open questions].
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Anagnostopoulos I and Zamò A
- Subjects
- Humans, Lymphoma, B-Cell diagnosis, Lymphoma, Follicular diagnosis
- Abstract
The 5th edition of the WHO classification (WHO-HAEM5) and the International Consensus Classification (ICC) have considerable overlap but also some distinct differences in categorizing indolent B‑cell lymphomas. Most differences with the expected impact on the daily diagnostic routine relate to follicular lymphoma (FL). Grading of FL remains mandatory only in the ICC; a diffuse growth pattern in an FL with > 15 blasts per high-power field (FL grade 3A) is not automatically classified as DLBCL according to WHO-HAEM5, and an FL subtype with unusual morphology (blastoid or large centrocyte) and biology is recognized as an entity only in the WHO-HAEM5. With the exception of B‑prolymphocytic leukemia, which is no longer acknowledged in WHO-HAEM5, there are only minor differences between both classifications and include updated names of entities, improved diagnostic criteria, and upgrades from provisional to definite entities., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)
- Published
- 2023
- Full Text
- View/download PDF
137. Routine application of the Lymph2Cx assay for the subclassification of aggressive B-cell lymphoma: report of a prospective real-world series.
- Author
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Zamò A, Gerhard-Hartmann E, Ott G, Anagnostopoulos I, Scott DW, Rosenwald A, and Rauert-Wunderlich H
- Subjects
- Humans, In Situ Hybridization, Fluorescence, Prospective Studies, Germinal Center pathology, RNA metabolism, RNA therapeutic use, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse genetics
- Abstract
The subclassification of diffuse large B-cell lymphoma (DLBCL) into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes has become mandatory in the 2017 update of the WHO classification of lymphoid neoplasms and will continue to be used in the WHO 5
th edition. The RNA-based Lymph2Cx assay has been validated as a reliable surrogate of high-throughput gene expression profiling assays for distinguishing between GCB and ABC DLBCL and provides reliable results from formalin-fixed, paraffin-embedded (FFPE) material. This test has been previously used in clinical trials, but experience from real-world routine application is rare. We routinely applied the Lymph2Cx assay to day-to-day diagnostics on a series of 147 aggressive B-cell lymphoma cases and correlated our results with the immunohistochemical subclassification using the Hans algorithm and fluorescence in situ hybridization findings using break-apart probes for MYC, BCL2, and BCL6. The routine use of the Lymph2Cx assay had a high technical success rate (94.6%) with a low rate of failure due to poor material and/or RNA quality. The Lymph2Cx assay was discordant with the Hans algorithm in 18% (23 of 128 cases). Discordant cases were mainly classified as GCB by the Hans algorithm and as ABC by Lymph2Cx (n = 11, 8.6%). Only 5 cases (3.9%) were classified as non-GCB by the Hans algorithm and as GCB by Lymph2Cx. Additionally, 5.5% of cases (n = 7) were left unclassified by Lymph2Cx, whereas they were defined as GCB (n = 4) or non-GCB (n = 3) by the Hans algorithm. Our data support the routine applicability of the Lymph2Cx assay., (© 2022. The Author(s).)- Published
- 2022
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138. Follicular lymphoma subgroups with and without t(14;18) differ in their N-glycosylation pattern and IGHV usage.
- Author
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Leich E, Maier C, Bomben R, Vit F, Bosi A, Horn H, Gattei V, Ott G, Rosenwald A, and Zamò A
- Subjects
- Cohort Studies, Glycosylation, High-Throughput Nucleotide Sequencing, Humans, Lymphoma, Follicular genetics
- Abstract
We previously reported that t(14;18)-negative follicular lymphomas (FL) show a clear reduction of newly acquired N-glycosylation sites (NANGS) in immunoglobulin genes. We therefore aimed to investigate in-depth the occurrence of NANGS in a larger cohort of t(14;18)-positive and t(14;18)-negative FL, including early (I/II) and advanced (III/IV) stage treatment-naive and relapsed tumors. The clonotype was determined by using a next-generation sequencing approach in a series of 68 FL with fresh frozen material [36 t(14;18) positive and 32 t(14;18) negative]. The frequency of NANGS differed considerably between t(14;18)-positive and t(14;18)-negative FL stage III/IV, but no difference was observed among t(14;18)-positive and t(14;18)-negative FL stage I/II. The introduction of NANGS in all t(14;18)-negative clinical subgroups occurred significantly more often in the FR3 region. Moreover, t(14;18)-negative treatment-naive FL, specifically those with NANGS, showed a strong bias for IGHV4-34 usage compared with t(14;18)-positive treatment-naive cases with NANGS; IGHV4-34 usage was never recorded in relapsed FL. In conclusion, subgroups of t(14;18)-negative FL might use different mechanisms of B-cell receptor stimulation compared with the lectin-mediated binding described in t(14;18)-positive FL, including responsiveness to autoantigens as indicated by biased IGHV4-34 usage and strong NANGS enrichment in FR3., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
139. KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study.
- Author
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Ferrero S, Rossi D, Rinaldi A, Bruscaggin A, Spina V, Eskelund CW, Evangelista A, Moia R, Kwee I, Dahl C, Di Rocco A, Stefoni V, Diop F, Favini C, Ghione P, Mahmoud AM, Schipani M, Kolstad A, Barbero D, Novero D, Paulli M, Zamò A, Jerkeman M, da Silva MG, Santoro A, Molinari A, Ferreri A, Grønbæk K, Piccin A, Cortelazzo S, Bertoni F, Ladetto M, and Gaidano G
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Humans, Mutation, Prognosis, Prospective Studies, Transplantation, Autologous, DNA-Binding Proteins genetics, Hematopoietic Stem Cell Transplantation, Lymphoma, Mantle-Cell diagnosis, Lymphoma, Mantle-Cell drug therapy, Lymphoma, Mantle-Cell genetics, Neoplasm Proteins genetics, Tumor Suppressor Protein p53 genetics
- Abstract
In recent years, the outcome of mantle cell lymphoma (MCL) has improved, especially in younger patients, receiving cytarabine-containing chemoimmunotherapy and autologous stem cell transplantation. Nevertheless, a proportion of MCL patients still experience early failure. To identify biomarkers anticipating failure of intensive chemotherapy in MCL, we performed target resequencing and DNA profiling of purified tumor samples collected from patients enrolled in the prospective FIL-MCL0208 phase 3 trial (high-dose chemoimmunotherapy followed by autologous transplantation and randomized lenalidomide maintenance). Mutations of KMT2D and disruption of TP53 by deletion or mutation associated with an increased risk of progression and death, both in univariate and multivariate analysis. By adding KMT2D mutations and TP53 disruption to the MIPI-c backbone, we derived a new prognostic index, the "MIPI-genetic" ("MIPI- g"). The "MIPI-g" improved the model discrimination ability compared to the MIPI-c alone, defining three risk groups: i) low-risk patients (4-year progression free survival and overall survival of 72.0% and 94.5%); ii) inter-mediate-risk patients (4-year progression free survival and overall survival of 42.2% and 65.8%) and iii) high-risk patients (4-year progression free survival and overall survival of 11.5% and 44.9%). Our results: i) confirm that TP53 disruption identifies a high-risk population characterized by poor sensitivity to conventional or intensified chemotherapy; ii) provide the pivotal evidence that patients harboring KMT2D mutations share the same poor outcome as patients harboring TP53 disruption; and iii) allow to develop a tool for the identification of high-risk MCL patients for whom novel therapeutic strategies need to be investigated. ( Trial registered at clinicaltrials.gov identifier: NCT02354313 )., (Copyright© 2020 Ferrata Storti Foundation.)
- Published
- 2020
- Full Text
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140. A B-cell receptor-related gene signature predicts response to ibrutinib treatment in mantle cell lymphoma cell lines.
- Author
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D'Agaro T, Zucchetto A, Vit F, Bittolo T, Tissino E, Rossi FM, Degan M, Zaja F, Bulian P, Bo MD, Ferrero S, Ladetto M, Zamò A, Gattei V, and Bomben R
- Subjects
- Adenine analogs & derivatives, Agammaglobulinaemia Tyrosine Kinase genetics, Antineoplastic Agents pharmacology, Biomarkers, Tumor genetics, CD79 Antigens genetics, Cell Line, Tumor, Class I Phosphatidylinositol 3-Kinases genetics, Gene Expression Regulation, Neoplastic, Humans, Immunotherapy, Leukocytes, Mononuclear cytology, Lymphoma, Mantle-Cell drug therapy, Neoplasm Recurrence, Local, Piperidines, Prognosis, Progression-Free Survival, Proto-Oncogene Proteins c-akt genetics, Proto-Oncogene Proteins c-bcl-2 genetics, Randomized Controlled Trials as Topic, Recurrence, Stem Cell Transplantation, Syk Kinase genetics, Treatment Outcome, Gene Expression Profiling, Lymphoma, Mantle-Cell genetics, Pyrazoles pharmacology, Pyrimidines pharmacology, Receptors, Antigen, B-Cell genetics
- Published
- 2019
- Full Text
- View/download PDF
141. slan + Monocytes and Macrophages Mediate CD20-Dependent B-cell Lymphoma Elimination via ADCC and ADCP.
- Author
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Vermi W, Micheletti A, Finotti G, Tecchio C, Calzetti F, Costa S, Bugatti M, Calza S, Agostinelli C, Pileri S, Balzarini P, Tucci A, Rossi G, Furlani L, Todeschini G, Zamò A, Facchetti F, Lorenzi L, Lonardi S, and Cassatella MA
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antibody-Dependent Cell Cytotoxicity drug effects, Antigens, CD20 immunology, Antigens, CD20 metabolism, Antineoplastic Agents, Immunological therapeutic use, Biopsy, Cells, Cultured, Child, Child, Preschool, Cohort Studies, Cytophagocytosis immunology, Female, Humans, Leukocytes, Mononuclear, Lymph Nodes cytology, Lymph Nodes immunology, Lymph Nodes pathology, Lymphoma, Large B-Cell, Diffuse immunology, Lymphoma, Large B-Cell, Diffuse pathology, Macrophages drug effects, Macrophages metabolism, Male, Middle Aged, Monocytes drug effects, Monocytes metabolism, Primary Cell Culture, Retrospective Studies, Rituximab pharmacology, Rituximab therapeutic use, Tumor Microenvironment drug effects, Tumor Microenvironment immunology, Tumor Suppressor Proteins metabolism, Young Adult, Antibody-Dependent Cell Cytotoxicity immunology, Antineoplastic Agents, Immunological pharmacology, Cytophagocytosis drug effects, Lymphoma, Large B-Cell, Diffuse drug therapy, Macrophages immunology, Monocytes immunology
- Abstract
Terminal tissue differentiation and function of slan
+ monocytes in cancer is largely unexplored. Our recent studies demonstrated that slan+ monocytes differentiate into a distinct subset of dendritic cells (DC) in human tonsils and that slan+ cells colonize metastatic carcinoma-draining lymph nodes. Herein, we report by retrospective analysis of multi-institutional cohorts that slan+ cells infiltrate various types of non-Hodgkin lymphomas (NHL), particularly the diffuse large B-cell lymphoma (DLBCL) group, including the most aggressive, nodal and extranodal, forms. Nodal slan+ cells displayed features of either immature DC or macrophages, in the latter case ingesting tumor cells and apoptotic bodies. We also found in patients with DLBCL that peripheral blood slan+ monocytes, but not CD14+ monocytes, increased in number and displayed highly efficient rituximab-mediated antibody-dependent cellular cytotoxicity, almost equivalent to that exerted by NK cells. Notably, slan+ monocytes cultured in conditioned medium from nodal DLBCL (DCM) acquired a macrophage-like phenotype, retained CD16 expression, and became very efficient in rituximab-mediated antibody-dependent cellular phagocytosis (ADCP). Macrophages derived from DCM-treated CD14+ monocytes performed very efficient rituximab-mediated ADCP, however, using different FcγRs from those used by slan+ macrophages. Our observations shed new light on the complexity of the immune microenvironment of DLBCL and demonstrate plasticity of slan+ monocytes homing to cancer tissues. Altogether, data identify slan+ monocytes and macrophages as prominent effectors of antibody-mediated tumor cell targeting in patients with DLBCL. Significance: slan+ monocytes differentiate into macrophages that function as prominent effectors of antibody-mediated tumor cell targeting in lymphoma. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/13/3544/F1.large.jpg Cancer Res; 78(13); 3544-59. ©2018 AACR ., (©2018 American Association for Cancer Research.)- Published
- 2018
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142. MicroRNA signatures and Foxp3 + cell count correlate with relapse occurrence in follicular lymphoma.
- Author
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Malpeli G, Barbi S, Greco C, Zupo S, Bertolaso A, Scupoli MT, Krampera M, Kamga PT, Croce CM, Scarpa A, and Zamò A
- Abstract
First line drug treatment of follicular lymphoma (FL) patients is followed by a highly variable disease-free time before relapse in about one third of patients. No molecular marker is able to predict efficiently the risk of relapse. We investigated the expression profile of microRNAs (miRNAs) by microarrays and of the tumor microenvironment by immunohistochemistry in 26 FLs and 12 reactive lymph nodes (rLN) as reference. Twenty-nine miRNAs were differentially expressed in FLs compared to rLNs and some of them discriminated grade 1 from 3a FLs. Both FLs and rLNs displayed molecular heterogeneity. FLs grouped into two clusters mostly driven by the tumor T-cell content. Among 21 drug-treated FL patients with an average follow-up of 13.5 years, eight cases relapsed. Twenty-six miRNAs discriminated between relapsed and non-relapsed FLs. Ten miRNAs also correlated with Foxp3
+ cells number. Notably, Foxp3+ cells were significantly less in relapsed patients and lower Foxp3+ cell number associated with shorter time-to-relapse. Foxp3+ cells did not co-expressed follicular helper T-cell markers and were therefore classified as regulatory T cells rather than follicular regulatory T-cells. These findings introduce new knowledge about the relationship between miRNA alterations and infiltrating immune cells and show that Foxp3+ cells might be predictive of disease relapse., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.- Published
- 2018
- Full Text
- View/download PDF
143. Establishment of the MAVER-1 cell line, a model for leukemic and aggressive mantle cell lymphoma.
- Author
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Zamò A, Ott G, Katzenberger T, Adam P, Parolini C, Scarpa A, Lestani M, Menestrina F, and Chilosi M
- Subjects
- Aged, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 14, Gene Rearrangement, Genes, myc, Humans, Immunophenotyping, Leukemia pathology, Male, Mutation, Translocation, Genetic, Cell Line, Tumor, Lymphoma, Mantle-Cell pathology
- Abstract
Background and Objectives: Mantle cell lymphoma (MCL) cell lines are difficult to generate; only nine lines have been described so far and few of them have been thoroughly characterized., Design and Methods: We established MAVER-1, a new MCL cell line, obtained from a leukemic MCL harboring both a t(11;14) translocation and a MYC rearrangement, and used immunohistochemistry, flow cytometry, molecular biology and cytogenetic techniques in order to characterize the cell line precisely., Results: By immunohistochemistry and flow cytometry MAVER-1 displayed a classical MCL phenotype (IgM+, l+, CD5+, CD10-, CD19+, CD20+, CD23-, CD79a+, cyclin D1+) and genetic analysis showed a typical V/D/J rearrangement with naïve mutational status. According to both classic cytogenetic analysis and spectral karyotyping, MAVER-1 harbored the t(11;14) translocation associated with a complex karyotype. Molecular analysis by polymerase chain reactions showed that the t(11;14) breakpoint is within the major translocation cluster. Other important abnormalities of MAVER-1 include TP53 gene inactivation by a combined mutation of exon 8 and chromosome 17p13 deletion, ATM deletion, 8q24 (MYC) rearrangement and 8p22 deletion., Interpretation and Conclusions: The new cell line will be useful for in vitro studies regarding MCL pathogenesis and drug sensitivity, as well as a diagnostic control material.
- Published
- 2006
144. HHV-8 and EBV are not commonly found in idiopathic pulmonary fibrosis.
- Author
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Zamò A, Poletti V, Reghellin D, Montagna L, Pedron S, Piccoli P, and Chilosi M
- Subjects
- Adult, Aged, Diagnosis, Differential, Epstein-Barr Virus Infections diagnosis, Epstein-Barr Virus Infections virology, Female, Herpesviridae Infections diagnosis, Herpesviridae Infections virology, Humans, Immunohistochemistry, In Situ Hybridization, Lung Diseases, Interstitial diagnosis, Lung Diseases, Interstitial virology, Male, Middle Aged, Polymerase Chain Reaction, Pulmonary Fibrosis pathology, Antibodies, Viral analysis, DNA, Viral analysis, Herpesvirus 4, Human genetics, Herpesvirus 4, Human immunology, Herpesvirus 8, Human genetics, Herpesvirus 8, Human immunology, Pulmonary Fibrosis virology
- Abstract
Background and Aim of the Work: Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia (IPF/UIP) is a diffuse and progressive lung disease whose pathogenesis is incompletely understood. Recently, the presence of Herpesvirus-specific DNA was detected in the large majority of cases of a series of IPF/UIP and other lung interstitial diseases. We have therefore tested our own IPF/UIP series for the presence of HHV-8 and EBV proteins., Methods: We used a variety of sensitive technologies including immunohistochemistry with NCL-HHV8-LNA and EBV-LMP1 antibodies, as well as of EBV RNA (EBER) by in-situ hybridisation; the presence of HHV-8 and EBV DNA was also investigated by means of PCR and subsequent analysis using a microfluidic apparatus., Results: Despite the good sample quality, immunohistochemical, in-situ hybridisation and PCR results were negative for both EBV and HHV-8., Conclusions: We conclude that EBV and HHV-8 are not involved in the pathogenesis of IPF/UIP.
- Published
- 2005
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