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Author Livio Trentin

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Hexokinase 2 displacement from mitochondria-associated membranes prompts Ca2+ -dependent death of cancer cells.

Francesco Ciscato, Riccardo Filadi, Ionica Masgras, Marco Pizzi, Oriano Marin, Nunzio Damiano, Paola Pizzo, Alessandro Gori, Federica Frezzato, Federica Chiara, Livio Trentin, Paolo Bernardi, Andrea Rasola,

Cancer cells undergo changes in metabolic and survival pathways that increase their malignancy. Isoform 2 of the glycolytic enzyme hexokinase (HK2) enhances both glucose metabolism and resistance to death stimuli in many neoplastic cell types. Here, we observe that HK2 locates at mitochondria-endoplasmic reticulum (ER) contact sites called MAMs (mitochondria-associated ... Read more >>

EMBO Rep. (EMBO reports)
[2020, :e49117]

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The Bruton tyrosine kinase inhibitor ibrutinib improves anti-MAG antibody polyneuropathy.

Francesca Castellani, Andrea Visentin, Marta Campagnolo, Alessandro Salvalaggio, Mario Cacciavillani, Cinzia Candiotto, Roberta Bertorelle, Livio Trentin, Chiara Briani,

OBJECTIVE:To assess whether neuropathy with anti-myelin-associated glycoprotein (MAG) antibody may improve after treatment with ibrutinib, an oral inhibitor of Bruton tyrosine kinase, we prospectively treated with ibrutinib a cohort of 3 patients with anti-MAG neuropathy and Waldenström macroglobulinemia (WM). METHODS:All 3 patients underwent bone marrow biopsy showing WM, with MYD88 ... Read more >>

Neurol Neuroimmunol Neuroinflamm (Neurology(R) neuroimmunology & neuroinflammation)
[2020, 7(4):]

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Frontline treatment with the combination obinutuzumab ± chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group.

Yair Herishanu, Adir Shaulov, Riva Fineman, Sandra Bašić-Kinda, Ariel Aviv, Ewa Wasik-Szczepanek, Ozren Jaksic, Mihnea Zdrenghea, Uri Greenbaum, Inga Mandac, Martin Simkovic, Marta Morawska, Ohad Benjamini, Martin Spacek, Anatoly Nemets, Osnat Bairey, Livio Trentin, Rosa Ruchlemer, Luca Laurenti, Oana Stanca Ciocan, Michael Doubek, Lev Shvidel, Nagib Dali, Fátima Mirás, Anne De Meûter, Maria Dimou, Francesca R Mauro, Marta Coscia, Horia Bumbea, Róbert Szász, Tamar Tadmor, Odit Gutwein, Massimo Gentile, Lydia Scarfò, Alessandra Tedeschi, Paolo Sportoletti, Eva Gimeno Vázquez, Juan Marquet, Sarit Assouline, Maria Papaioannou, Andrei Braester, Luciano Levato, Michael Gregor, Gian M Rigolin, Javier Loscertales, Angeles Medina Perez, Marten R Nijziel, Viola M Popov, Rosa Collado, Irma Slavutsky, Gilad Itchaki, Shimrit Ringelstein, Neta Goldschmidt, Chava Perry, Shai Levi, Aaron Polliack, Paolo Ghia,

In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with ... Read more >>

Am. J. Hematol. (American journal of hematology)
[2020, 95(6):604-611]

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In Chronic Lymphocytic Leukemia the JAK2/STAT3 Pathway Is Constitutively Activated and Its Inhibition Leads to CLL Cell Death Unaffected by the Protective Bone Marrow Microenvironment.

Filippo Severin, Federica Frezzato, Andrea Visentin, Veronica Martini, Valentina Trimarco, Samuela Carraro, Elena Tibaldi, Anna Maria Brunati, Francesco Piazza, Gianpietro Semenzato, Monica Facco, Livio Trentin,

The bone marrow microenvironment promotes proliferation and drug resistance in chronic lymphocytic leukemia (CLL). Although ibrutinib is active in CLL, it is rarely able to clear leukemic cells protected by bone marrow mesenchymal stromal cells (BMSCs) within the marrow niche. We investigated the modulation of JAK2/STAT3 pathway in CLL by ... Read more >>

Cancers (Basel) (Cancers)
[2019, 11(12):]

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DNA methylation profiles in chronic lymphocytic leukemia patients treated with chemoimmunotherapy.

Maria Tsagiopoulou, Nikos Papakonstantinou, Theodoros Moysiadis, Larry Mansouri, Viktor Ljungström, Martí Duran-Ferrer, Andigoni Malousi, Ana C Queirós, Karla Plevova, Sujata Bhoi, Panagoula Kollia, David Oscier, Achilles Anagnostopoulos, Livio Trentin, Matthias Ritgen, Sarka Pospisilova, Niki Stavroyianni, Paolo Ghia, Jose I Martin-Subero, Christiane Pott, Richard Rosenquist, Kostas Stamatopoulos,

BACKGROUND:In order to gain insight into the contribution of DNA methylation to disease progression of chronic lymphocytic leukemia (CLL), using 450K Illumina arrays, we determined the DNA methylation profiles in paired pre-treatment/relapse samples from 34 CLL patients treated with chemoimmunotherapy, mostly (n = 31) with the fludarabine-cyclophosphamide-rituximab (FCR) regimen. RESULTS:The ... Read more >>

Clin Epigenetics (Clinical epigenetics)
[2019, 11(1):177]

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New responsibilities for aged kinases in B-lymphomas.

Francesco Piazza, Sabrina Manni, Arash Arjomand, Andrea Visentin, Livio Trentin, Gianpietro Semenzato,

The knowledge accumulated over the last decade on B-cell-derived non-Hodgkin lymphoma (B-NHL) pathogenesis has led to the identification of several molecular abnormalities, opening new perspectives in the design of novel therapies. Indeed, drugs targeting specific biochemical pathways critical for B-NHL cell survival, proliferation, and fitness within the malignant microenvironment are ... Read more >>

Hematol Oncol (Hematological oncology)
[2020, 38(1):3-11]

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Hexokinase 2 displacement from mitochondria-associated membranes prompts Ca2+-dependent death of cancer cells

Francesco Ciscato, Riccardo Filadi, Ionica Masgras, Marco Pizzi, Oriano Marin, Nunzio Damiano, Paola Pizzo, Alessandro Gori, Federica Frezzato, Livio Trentin, Paolo Bernardi, Andrea Rasola,

Abstract Cancer cells undergo changes in metabolic and survival pathways that increase their malignancy. Isoform 2 of the glycolytic enzyme hexokinase (HK2) enhances both glucose metabolism and resistance to death stimuli in many neoplastic cell types. Here we observe that HK2 locates at mitochondria-endoplasmic reticulum (ER) contact sites called MAMs ... Read more >>

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A scoring system to predict the risk of atrial fibrillation in chronic lymphocytic leukemia.

Andrea Visentin, Marina Deodato, Francesca R Mauro, Francesco Autore, Gianluigi Reda, Candida Vitale, Stefano Molica, Gian Matteo Rigolin, Francesco Piazza, Laura Cesini, Alessandra Tedeschi, Luca Laurenti, Ramona Cassin, Marta Coscia, Antonio Cuneo, Robin Foà, Gianpietro Semenzato, Livio Trentin,

Hematol Oncol (Hematological oncology)
[2019, 37(4):508-512]

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Venetoclax in CLL patients who progress after B-cell Receptor inhibitor treatment: a retrospective multi-centre Italian experience.

Idanna Innocenti, Francesca Morelli, Francesco Autore, Alfonso Piciocchi, Annamaria Frustaci, Francesca R Mauro, Luana Schiattone, Livio Trentin, Giovanni Del Poeta, Gianluigi Reda, Gian M Rigolin, Adalberto Ibatici, Stefania Ciolli, Marta Coscia, Paolo Sportoletti, Roberta Murru, Luciano Levato, Massimo Gentile, Giovanni D'Arena, Dimitar G Efremov, Alessandra Tedeschi, Lydia Scarfò, Antonio Cuneo, Robin Foà, Luca Laurenti,

Br. J. Haematol. (British journal of haematology)
[2019, 187(1):e8-e11]

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The combination of complex karyotype subtypes and IGHV mutational status identifies new prognostic and predictive groups in chronic lymphocytic leukaemia.

Andrea Visentin, Laura Bonaldi, Gian Matteo Rigolin, Francesca Romana Mauro, Annalisa Martines, Federica Frezzato, Silvia Imbergamo, Edoardo Scomazzon, Stefano Pravato, Maria Antonella Bardi, Maurizio Cavallari, Eleonora Volta, Francesco Cavazzini, Maurizio Nanni, Ilaria Del Giudice, Monica Facco, Anna Guarini, Gianpietro Semenzato, Robin Foà, Antonio Cuneo, Livio Trentin,

BACKGROUND:Complex karyotype (CK) is a heterogeneous category with a negative impact in chronic lymphocytic leukaemia (CLL). Our group has recently reported that CK patients with major structural abnormalities (i.e. CK2) are characterised by a worse prognosis, as compared to other lesions within CK(CK1). METHODS:We performed a multicentre retrospective study to ... Read more >>

Br. J. Cancer (British journal of cancer)
[2019, 121(2):150-156]

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Elevated Lactate Dehydrogenase Has Prognostic Relevance in Treatment-Naïve Patients Affected by Chronic Lymphocytic Leukemia with Trisomy 12.

Francesco Autore, Paolo Strati, Idanna Innocenti, Francesco Corrente, Livio Trentin, Agostino Cortelezzi, Carlo Visco, Marta Coscia, Antonio Cuneo, Alessandro Gozzetti, Francesca Romana Mauro, Anna Maria Frustaci, Massimo Gentile, Fortunato Morabito, Stefano Molica, Paolo Falcucci, Giovanni D'Arena, Roberta Murru, Donatella Vincelli, Dimitar G Efremov, Antonietta Ferretti, Gian Matteo Rigolin, Candida Vitale, Maria Chiara Tisi, Gianluigi Reda, Andrea Visentin, Simona Sica, Robin Foà, Alessandra Ferrajoli, Luca Laurenti,

Chronic Lymphocytic Leukemia (CLL) patients with +12 have been reported to have specific clinical and biologic features. We performed an analysis of the association between demographic; clinical; laboratory; biologic features and outcome in CLL patients with +12 to identify parameters predictive of disease progression; time to treatment; and survival. The ... Read more >>

Cancers (Basel) (Cancers)
[2019, 11(7):]

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Olaptesed pegol (NOX-A12) with bendamustine and rituximab: a phase IIa study in patients with relapsed/refractory chronic lymphocytic leukemia.

Michael Steurer, Marco Montillo, Lydia Scarfò, Francesca R Mauro, Johannes Andel, Sophie Wildner, Livio Trentin, Ann Janssens, Sonja Burgstaller, Anna Frömming, Thomas Dümmler, Kai Riecke, Matthias Baumann, Diana Beyer, Stéphanie Vauléon, Paolo Ghia, Robin Foà, Federico Caligaris-Cappio, Marco Gobbi,

Olaptesed pegol (NOX-A12) is a pegylated structured L-oligoribonucleotide that binds and neutralizes CXCL12, a chemokine tightly regulating the life cycle of chronic lymphocytic leukemia cells. The resulting inhibition of CXCR4 and CXCR7 signaling reduces the protective activity of the bone marrow and lymph node microenvironment. CXCL12 inhibition mobilizes chronic lymphocytic ... Read more >>

Haematologica (Haematologica)
[2019, 104(10):2053-2060]

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HSP70/HSF1 axis, regulated via a PI3K/AKT pathway, is a druggable target in chronic lymphocytic leukemia.

Federica Frezzato, Flavia Raggi, Veronica Martini, Filippo Severin, Valentina Trimarco, Andrea Visentin, Edoardo Scomazzon, Benedetta Accordi, Silvia Bresolin, Francesco Piazza, Monica Facco, Giuseppe Basso, Gianpietro Semenzato, Livio Trentin,

Considering the role played by the heat shock protein of 70 kDa (HSP70) in cancer, we characterized this protein and its major regulator, the heat shock factor 1 (HSF1), in chronic lymphocytic leukemia (CLL). We found both HSP70 and HSF1 overexpressed in CLL patients, correlated to poor prognosis and abnormally localized ... Read more >>

Int. J. Cancer (International journal of cancer)
[2019, 145(11):3089-3100]

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Prognostic and Predictive Effect of IGHV Mutational Status and Load in Chronic Lymphocytic Leukemia: Focus on FCR and BR Treatments.

Andrea Visentin, Monica Facco, Carmela Gurrieri, Elisa Pagnin, Veronica Martini, Silvia Imbergamo, Federica Frezzato, Valentina Trimarco, Filippo Severin, Flavia Raggi, Edoardo Scomazzon, Stefano Pravato, Francesco Piazza, Gianpietro Semenzato, Livio Trentin,

BACKGROUND:Most important markers in chronic lymphocytic leukemia (CLL) are TP53 abnormalities, including mutations and deletions, and the mutational status of immunoglobulin heavy chain (IGHV) genes. However, some recent publications suggest that the IGHV mutational load could have a prognostic effect on CLL patients. PATIENTS AND METHODS:We performed a single-center retrospective ... Read more >>

Clin Lymphoma Myeloma Leuk (Clinical lymphoma, myeloma & leukemia)
[2019, 19(10):678-685.e4]

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p66Shc deficiency in the Eμ-TCL1 mouse model of chronic lymphocytic leukemia enhances leukemogenesis by altering the chemokine receptor landscape.

Laura Patrussi, Nagaja Capitani, Cristina Ulivieri, Noemi Manganaro, Massimo Granai, Francesca Cattaneo, Anna Kabanova, Lucia Mundo, Stefania Gobessi, Federica Frezzato, Andrea Visentin, Francesca Finetti, Pier Giuseppe Pelicci, Mario M D'Elios, Livio Trentin, Gianpietro Semenzato, Lorenzo Leoncini, Dimitar G Efremov, Cosima T Baldari,

The Shc family adaptor p66Shc acts as a negative regulator of proliferative and survival signals triggered by the B-cell receptor and, by enhancing the production of reactive oxygen species, promotes oxidative stress-dependent apoptosis. Additionally, p66Shc controls the expression and function of chemokine receptors that regulate lymphocyte traffic. Chronic lymphocytic leukemia ... Read more >>

Haematologica (Haematologica)
[2019, 104(10):2040-2052]

Cited: 2 times

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Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact.

Panagiotis Baliakas, Sabine Jeromin, Michalis Iskas, Anna Puiggros, Karla Plevova, Florence Nguyen-Khac, Zadie Davis, Gian Matteo Rigolin, Andrea Visentin, Aliki Xochelli, Julio Delgado, Fanny Baran-Marszak, Evangelia Stalika, Pau Abrisqueta, Kristina Durechova, George Papaioannou, Virginie Eclache, Maria Dimou, Theodoros Iliakis, Rosa Collado, Michael Doubek, M Jose Calasanz, Neus Ruiz-Xiville, Carolina Moreno, Marie Jarosova, Alexander C Leeksma, Panayiotis Panayiotidis, Helena Podgornik, Florence Cymbalista, Achilles Anagnostopoulos, Livio Trentin, Niki Stavroyianni, Fred Davi, Paolo Ghia, Arnon P Kater, Antonio Cuneo, Sarka Pospisilova, Blanca Espinet, Anastasia Athanasiadou, David Oscier, Claudia Haferlach, Kostas Stamatopoulos, ,

Recent evidence suggests that complex karyotype (CK) defined by the presence of ≥3 chromosomal aberrations (structural and/or numerical) identified by using chromosome-banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges toward the routine clinical application of CBA remain. In a retrospective study ... Read more >>

Blood (Blood)
[2019, 133(11):1205-1216]

Cited: 2 times

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Cortactin expression in non-Hodgkin B-cell lymphomas: a new marker for the differential diagnosis between chronic lymphocytic leukemia and mantle cell lymphoma.

Marco Pizzi, Livio Trentin, Andrea Visentin, Deborah Saraggi, Veronica Martini, Vincenza Guzzardo, Simona Righi, Federica Frezzato, Francesco Piazza, Elena Sabattini, Gianpietro Semenzato, Massimo Rugge,

Cortactin is a cytoskeletal-remodeling adaptor protein, playing an oncogenic role in solid tumors. Little is known on cortactin expression in non-Hodgkin B-cell lymphomas (B-NHLs). The present study aimed to characterize cortactin expression in B-NHLs and to assess its role in the differential diagnosis of such entities. Cortactin protein expression was ... Read more >>

Hum. Pathol. (Human pathology)
[2019, 85:251-259]

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Mitochondrial apoptosis is induced by Alkoxy phenyl-1-propanone derivatives through PP2A-mediated dephosphorylation of Bad and Foxo3A in CLL.

Mario Angelo Pagano, Elena Tibaldi, Pierfrancesco Molino, Federica Frezzato, Valentina Trimarco, Monica Facco, Giuseppe Zagotto, Giovanni Ribaudo, Luigi Leanza, Roberta Peruzzo, Ildikò Szabò, Andrea Visentin, Martina Frasson, Gianpietro Semenzato, Livio Trentin, Anna Maria Brunati,

Protein phosphatase 2 A (PP2A) is a tumour suppressor whose strong inhibition underlies the phosphorylation-dependent, anti-apoptotic mechanisms in Chronic Lymphocytic Leukemia (CLL). Inactivation of PP2A is due to the cooperative action of the phosphorylation of Y307 of its catalytic subunit by the aberrant cytosolic pool of the Src Family Kinase ... Read more >>

Leukemia (Leukemia)
[2019, 33(5):1148-1160]

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Ibrutinib Therapy Releases Leukemic Surface IgM from Antigen Drive in Chronic Lymphocytic Leukemia Patients.

Samantha Drennan, Giorgia Chiodin, Annalisa D'Avola, Ian Tracy, Peter W Johnson, Livio Trentin, Andrew J Steele, Graham Packham, Freda K Stevenson, Francesco Forconi,

PURPOSE:In chronic lymphocytic leukemia (CLL), disease progression associates with surface IgM (sIgM) levels and signaling capacity. These are variably downmodulated in vivo and recover in vitro, suggesting a reversible influence of tissue-located antigen. Therapeutic targeting of sIgM function via ibrutinib, an inhibitor of Bruton tyrosine kinase (BTK), causes inhibition and ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2019, 25(8):2503-2512]

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Abnormal regulation of BCR signalling by c-Cbl in chronic lymphocytic leukaemia.

Veronica Martini, Federica Frezzato, Filippo Severin, Flavia Raggi, Valentina Trimarco, Leonardo Martinello, Rosa Molfetta, Andrea Visentin, Monica Facco, Gianpietro Semenzato, Rossella Paolini, Livio Trentin,

Abnormalities of molecules involved in signal transduction pathways are connected to Chronic Lymphocytic Leukemia (CLL) pathogenesis and a critical role has been already ascribed to B-Cell Receptor (BCR)-Lyn axis. E3 ubiquitin ligase c-Cbl, working together with adapter protein CIN85, controls the degradation of protein kinases involved in BCR signaling. To ... Read more >>

Oncotarget (Oncotarget)
[2018, 9(63):32219-32231]

Cited: 1 time

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Dabigatran in ibrutinib-treated patients with atrial fibrillation and lymphoproliferative diseases: Experience of 4 cases.

Andrea Visentin, Elena Campello, Edoardo Scomazzon, Luca Spiezia, Silvia Imbergamo, Stefano Pravato, Francesco Piazza, Gianpietro Semenzato, Paolo Simioni, Livio Trentin,

Hematol Oncol (Hematological oncology)
[2018, 36(5):801-803]

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Italian real life experience with ibrutinib: results of a large observational study on 77 relapsed/refractory mantle cell lymphoma.

Alessandro Broccoli, Beatrice Casadei, Alice Morigi, Federico Sottotetti, Manuel Gotti, Michele Spina, Stefano Volpetti, Simone Ferrero, Francesco Spina, Francesco Pisani, Michele Merli, Carlo Visco, Rossella Paolini, Vittorio Ruggero Zilioli, Luca Baldini, Nicola Di Renzo, Patrizia Tosi, Nicola Cascavilla, Stefano Molica, Fiorella Ilariucci, Gian Matteo Rigolin, Francesco D'Alò, Anna Vanazzi, Elisa Santambrogio, Roberto Marasca, Lucia Mastrullo, Claudia Castellino, Giovanni Desabbata, Ilaria Scortechini, Livio Trentin, Lucia Morello, Lisa Argnani, Pier Luigi Zinzani,

Although sometimes presenting as an indolent lymphoma, mantle cell lymphoma (MCL) is an aggressive disease, hardly curable with standard chemo-immunotherapy. Current approaches have greatly improved patients' outcomes, nevertheless the disease is still characterized by high relapse rates. Before approval by EMA, Italian patients with relapsed/refractory MCL were granted ibrutinib early ... Read more >>

Oncotarget (Oncotarget)
[2018, 9(34):23443-23450]

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BCR kinase inhibitors, idelalisib and ibrutinib, are active and effective in Richter syndrome.

Andrea Visentin, Silvia Imbergamo, Edoardo Scomazzon, Stefano Pravato, Federica Frezzato, Laura Bonaldi, Marco Pizzi, Stefania Vio, Michele Gregianin, Marta Burei, Monica Facco, Gianpietro Semenzato, Francesco Piazza, Livio Trentin,

Br. J. Haematol. (British journal of haematology)
[2019, 185(1):193-197]

Cited: 1 time

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In chronic lymphocytic leukaemia with complex karyotype, major structural abnormalities identify a subset of patients with inferior outcome and distinct biological characteristics.

Gian Matteo Rigolin, Elena Saccenti, Emanuele Guardalben, Maurizio Cavallari, Luca Formigaro, Barbara Zagatti, Andrea Visentin, Francesca R Mauro, Enrico Lista, Cristian Bassi, Laura Lupini, Francesca Maria Quaglia, Antonio Urso, Maria Antonella Bardi, Laura Bonaldi, Eleonora Volta, Elisa Tammiso, Caterina Ilari, Luciana Cafforio, Aurora Melandri, Francesco Cavazzini, Massimo Negrini, Gianpietro Semenzato, Livio Trentin, Robin Foà, Antonio Cuneo,

Complex karyotype (CK) is a negative prognostic factor in chronic lymphocytic leukaemia (CLL). However, CK is a heterogeneous cytogenetic category. Unbalanced rearrangements were present in 73·3% of 90 CLL patients with CK (i.e. ≥3 chromosome aberrations in the same clone), and were associated with a shorter overall survival (P = 0·025) and ... Read more >>

Br. J. Haematol. (British journal of haematology)
[2018, 181(2):229-233]

Cited: 2 times

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Splenic marginal zone lymphoma with a de novo t(8;14)(q24;q32) and a prolymphocytoid evolution responsive to rituximab-bendamustine.

Greta Scapinello, Marco Pizzi, Stefania Vio, Mitja Nabergoj, Andrea Visentin, Annalisa Martines, Laura Bonaldi, Livio Trentin, Gianpietro Semenzato, Francesco Piazza,

Ann. Hematol. (Annals of hematology)
[2018, 97(10):2001-2003]

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