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Mara Compagno

Federico Gulluni, Miriam Martini, Maria Chiara De Santis, Carlo Cosimo Campa, Alessandra Ghigo, Jean Piero Margaria, Elisa Ciraolo, Irene Franco, Ugo Ala, Laura Annaratone, Davide Disalvatore, Giovanni Bertalot, Giuseppe Viale, Anna Noatynska, Mara Compagno, Sara Sigismund, Filippo Montemurro, Marcus Thelen, Fan Fan, Patrick Meraldi, Caterina Marchiò, Salvatore Pece, Anna Sapino, Roberto Chiarle, Pier Paolo Di Fiore, Emilio Hirsch
Proper organization of the mitotic spindle is key to genetic stability, but molecular components of inter-microtubule bridges that crosslink kinetochore fibers (K-fibers) are still largely unknown. Here we identify a kinase-independent function of class II phosphoinositide 3-OH kinase α (PI3K-C2α) acting as limiting scaffold protein organizing clathrin and TACC3 complex crosslinking K-fibers. Downregulation of PI3K-C2α causes spindle alterations, delayed anaphase onset, and aneuploidy, indicating that PI3K-C2α expression is required for genomic stability...
October 9, 2017: Cancer Cell
Mara Compagno, Qi Wang, Chiara Pighi, Taek-Chin Cheong, Fei-Long Meng, Teresa Poggio, Leng-Siew Yeap, Elif Karaca, Rafael B Blasco, Fernanda Langellotto, Chiara Ambrogio, Claudia Voena, Adrian Wiestner, Siddha N Kasar, Jennifer R Brown, Jing Sun, Catherine J Wu, Monica Gostissa, Frederick W Alt, Roberto Chiarle
Activation-induced cytidine deaminase (AID) is a B-cell-specific enzyme that targets immunoglobulin genes to initiate class switch recombination and somatic hypermutation. In addition, through off-target activity, AID has a much broader effect on genomic instability by initiating oncogenic chromosomal translocations and mutations involved in the development and progression of lymphoma. AID expression is tightly regulated in B cells and its overexpression leads to enhanced genomic instability and lymphoma formation...
February 23, 2017: Nature
Claudia Voena, Lydia M Varesio, Liye Zhang, Matteo Menotti, Teresa Poggio, Elena Panizza, Qi Wang, Valerio G Minero, Sharmila Fagoonee, Mara Compagno, Fiorella Altruda, Stefano Monti, Roberto Chiarle
A subset of Non-Small Cell Lung Carcinoma (NSCLC) carries chromosomal rearrangements involving the Anaplastic Lymphoma Kinase (ALK) gene. ALK-rearranged NSCLC are typically adenocarcinoma characterized by a solid signet-ring cell pattern that is frequently associated with a metastatic phenotype. Recent reports linked the presence of ALK rearrangement to an epithelial-mesenchymal transition (EMT) phenotype in NSCLC, but the extent and the mechanisms of an ALK-mediated EMT in ALK-rearranged NSCLC are largely unknown...
May 31, 2016: Oncotarget
Taek-Chin Cheong, Mara Compagno, Roberto Chiarle
Applications of the CRISPR-Cas9 system to edit the genome have widely expanded to include DNA gene knock-out, deletions, chromosomal rearrangements, RNA editing and genome-wide screenings. Here we show the application of CRISPR-Cas9 technology to edit the mouse and human immunoglobulin (Ig) genes. By delivering Cas9 and guide-RNA (gRNA) with retro- or lenti-virus to IgM(+) mouse B cells and hybridomas, we induce class-switch recombination (CSR) of the IgH chain to the desired subclass. Similarly, we induce CSR in all human B cell lines tested with high efficiency to targeted IgH subclass...
March 9, 2016: Nature Communications
Ramesh Choudhari, Valerio Giacomo Minero, Matteo Menotti, Roberta Pulito, Cord Brakebusch, Mara Compagno, Claudia Voena, Chiara Ambrogio, Roberto Chiarle
Increasing evidence suggests that Rho family GTPases could have a critical role in the biology of T-cell lymphoma. In ALK-rearranged anaplastic large cell lymphoma (ALCL), a specific subtype of T-cell lymphoma, the Rho family GTPases Cdc42 and Rac1 are activated by the ALK oncogenic activity. In vitro studies have shown that Cdc42 and Rac1 control rather similar phenotypes of ALCL biology such as the proliferation, survival, and migration of lymphoma cells. However, their role and possible redundancy in ALK-driven lymphoma development in vivo are still undetermined...
March 10, 2016: Blood
Roberto Chiarle, Yu Zhang, Richard L Frock, Susanna M Lewis, Benoit Molinie, Yu-Jui Ho, Darienne R Myers, Vivian W Choi, Mara Compagno, Daniel J Malkin, Donna Neuberg, Stefano Monti, Cosmas C Giallourakis, Monica Gostissa, Frederick W Alt
Whereas chromosomal translocations are common pathogenetic events in cancer, mechanisms that promote them are poorly understood. To elucidate translocation mechanisms in mammalian cells, we developed high-throughput, genome-wide translocation sequencing (HTGTS). We employed HTGTS to identify tens of thousands of independent translocation junctions involving fixed I-SceI meganuclease-generated DNA double-strand breaks (DSBs) within the c-myc oncogene or IgH locus of B lymphocytes induced for activation-induced cytidine deaminase (AID)-dependent IgH class switching...
September 30, 2011: Cell
Mara Compagno, Wei Keat Lim, Adina Grunn, Subhadra V Nandula, Manisha Brahmachary, Qiong Shen, Francesco Bertoni, Maurilio Ponzoni, Marta Scandurra, Andrea Califano, Govind Bhagat, Amy Chadburn, Riccardo Dalla-Favera, Laura Pasqualucci
Diffuse large B-cell lymphoma (DLBCL), the most common form of lymphoma in adulthood, comprises multiple biologically and clinically distinct subtypes including germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL. Gene expression profile studies have shown that its most aggressive subtype, ABC-DLBCL, is associated with constitutive activation of the NF-kappaB transcription complex. However, except for a small fraction of cases, it remains unclear whether NF-kappaB activation in these tumours represents an intrinsic program of the tumour cell of origin or a pathogenetic event...
June 4, 2009: Nature
Urban Novak, Andrea Rinaldi, Ivo Kwee, Subhadra V Nandula, Paola M V Rancoita, Mara Compagno, Michaela Cerri, Davide Rossi, Vundavalli V Murty, Emanuele Zucca, Gianluca Gaidano, Riccardo Dalla-Favera, Laura Pasqualucci, Govind Bhagat, Francesco Bertoni
Unique and shared cytogenetic abnormalities have been documented for marginal zone lymphomas (MZLs) arising at different sites. Recently, homozygous deletions of the chromosomal band 6q23, involving the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) gene, a negative regulator of NF-kappaB, were described in ocular adnexal MZL, suggesting a role for A20 as a tumor suppressor in this disease. Here, we investigated inactivation of A20 by DNA mutations or deletions in a panel of extranodal MZL (EMZL), nodal MZL (NMZL), and splenic MZL (SMZL)...
May 14, 2009: Blood
Laura Pasqualucci, Govind Bhagat, Mila Jankovic, Mara Compagno, Paula Smith, Masamichi Muramatsu, Tasuku Honjo, Herbert C Morse, Michel C Nussenzweig, Riccardo Dalla-Favera
Most human B cell non-Hodgkin's lymphomas (B-NHLs) derive from germinal centers (GCs), the structure in which B cells undergo somatic hypermutation (SHM) and class switch recombination (CSR) before being selected for high-affinity antibody production. The pathogenesis of B-NHL is associated with distinct genetic lesions, including chromosomal translocations and aberrant SHM, which arise from mistakes occurring during CSR and SHM. A direct link between these DNA remodeling events and GC lymphoma development, however, has not been demonstrated...
January 2008: Nature Genetics
Alberto Rocci, Irene Ricca, Chiara Dellacasa, Paolo Longoni, Mara Compagno, Roberto Francese, Chiara Lobetti Bodoni, Paola Manzini, Daniele Caracciolo, Mario Boccadoro, Dario Ferrero, Marco Ladetto, Carmelo Carlo-Stella, Corrado Tarella
OBJECTIVE: To investigate telomere length (TL) and hematopoietic progenitors in long-term survivors after high-dose chemotherapy and peripheral blood stem cell (PBSC) autograft. METHODS: Peripheral blood (PB) and bone marrow (BM) samples were obtained from 31 subjects in continuous complete remission from a high-risk lymphoma, at a median of 5.8 years (range: 1-11 years) since autograft. Most of them were grafted with large PBSC quantities (median CD34(+ve) cells/kg: 7 x 10(6))...
April 2007: Experimental Hematology
Laura Pasqualucci, Mara Compagno, Jane Houldsworth, Stefano Monti, Adina Grunn, Subhadra V Nandula, Jon C Aster, Vundavally V Murty, Margaret A Shipp, Riccardo Dalla-Favera
PR domain containing 1 with zinc finger domain (PRDM1)/B lymphocyte-induced maturation protein 1 (BLIMP1) is a transcriptional repressor expressed in a subset of germinal center (GC) B cells and in all plasma cells, and required for terminal B cell differentiation. The BLIMP1 locus lies on chromosome 6q21-q22.1, a region frequently deleted in B cell lymphomas, suggesting that it may harbor a tumor suppressor gene. We report here that the BLIMP1 gene is inactivated by structural alterations in 24% (8 out of 34) activated B cell-like diffuse large cell lymphoma (ABC-DLBCL), but not in GC B cell-like (n = 0/37) or unclassified (n = 0/21) DLBCL...
February 20, 2006: Journal of Experimental Medicine
Mara Compagno, Barbara Mantoan, Monica Astolfi, Mario Boccadoro, Marco Ladetto
The evaluation of minimal residual disease (MRD) is critical in the evaluation of treatments aimed at maximal cytoreduction in multiple myeloma (MM). Qualitative evaluation of MRD now has a 10-yr-long history, but it remains a relatively sophisticated procedure. More recently, real-time quantitative approaches have also been developed. These approaches allow a very effective monitoring of disease but introduce additional complexity and costs to the procedure. This chapter describes how we currently perform real-time polymerase chain reaction (PCR) in MM...
2005: Methods in Molecular Medicine
Marco Ladetto, Sonia Vallet, Andreas Trojan, Maria Dell'Aquila, Luigia Monitillo, Rosalba Rosato, Loredana Santo, Daniela Drandi, Alessandra Bertola, Patrizia Falco, Federica Cavallo, Irene Ricca, Federica De Marco, Barbara Mantoan, Beata Bode-Lesniewska, Gloria Pagliano, Roberto Francese, Alberto Rocci, Monica Astolfi, Mara Compagno, Sara Mariani, Laura Godio, Lydia Marino, Marina Ruggeri, Paola Omedè, Antonio Palumbo, Mario Boccadoro
Cyclooxygenase 2 (COX-2) is an inflammation-associated enzyme involved in the pathogenesis of many solid tumors, but little is known about its presence and role in hematologic neoplasms. Multiple myeloma (MM) is known to involve a deregulated cytokine network with secretion of inflammatory mediators. We thus decided to investigate the involvement of COX-2 in this neoplasm. Western blotting (WB) was used to evaluate 142 bone marrow (BM) specimens, including MM and monoclonal gammopathy of undetermined significance (MGUS)...
June 15, 2005: Blood
Marco Ladetto, Mara Compagno, Irene Ricca, Marco Pagano, Alberto Rocci, Monica Astolfi, Daniela Drandi, Paola Francia di Celle, Maria Dell'Aquila, Barbara Mantoan, Sonia Vallet, Gloria Pagliano, Federica De Marco, Roberto Francese, Loredana Santo, Alessandra Cuttica, Carlo Marinone, Mario Boccadoro, Corrado Tarella
In this study we investigated telomere restriction fragment (TRF) length in a panel of mature B-cell lymphoproliferative disorders (MBCLDs) and correlated this parameter with histology and histopathogenesis in relation to the germinal center (GC). We assessed 123 MBCLD samples containing 80% or more tumor cells. TRF length was evaluated by Southern blot analysis using a chemiluminescence-based assay. GC status was assessed through screening for stable and ongoing somatic mutations within the immunoglobulin heavy-chain genes...
June 15, 2004: Blood
Marco Ladetto, Barbara Mantoan, Irene Ricca, Monica Astolfi, Daniela Drandi, Mara Compagno, Sonia Vallet, Maria dell'Aquila, Alda Alfarano, Paola Rossatto, Alberto Rocci, Umberto Vitolo, Paolo Corradini, Mario Boccadoro, Corrado Tarella
OBJECTIVE: The aim of this study was to evaluate whether reappearance of polymerase chain reaction (PCR) positivity for the Bcl-2/IgH translocation following a phase of molecular remission in autografted follicular lymphoma (FL) patients is always associated with reappearance of the original neoplastic clone. PATIENTS AND METHODS: The molecular follow-up of 119 autografted Bcl-2/IgH positive patients was evaluated by nested PCR. In case of molecular recurrence, direct sequencing of involved rearrangements has been performed both at diagnosis and at the time of recurrence...
September 2003: Experimental Hematology
Marco Ladetto, Daniela Drandi, Mara Compagno, Monica Astolfi, Federica Volpato, Claudia Voena, Anna Novarino, Berardino Pollio, Alfredo Addeo, Irene Ricca, Patrizia Falco, Federica Cavallo, Sonia Vallet, Paolo Corradini, Alessandro Pileri, Giacomo Tamponi, Antonio Palumbo, Oscar Bertetto, Mario Boccadoro, Corrado Tarella
PURPOSE: To assess whether nonneoplastic Bcl-2/IgH rearrangements act as a confounding factor in the setting of minimal residual disease analysis by evaluating their incidence in a panel of lymphoma-free subjects, including cancer-free donors and chemotherapy-naive and chemotherapy-treated cancer patients. PATIENTS AND METHODS: A total of 501 nonlymphoma subjects have been assessed: 258 cancer-free patients and 243 patients with malignancies other than lymphoma, 112 of whom were chemotherapy-naive...
April 1, 2003: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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