6 results on '"Falcone, Antonietta"'
Number of results to display per page
Search Results
2. Rotation of nilotinib and imatinib for first-line treatment of chronic phase chronic myeloid leukemia
- Author
-
Gugliotta, Gabriele, Castagnetti, Fausto, Breccia, Massimo, Gozzini, Antonella, Usala, Emilio, Carella, Angelo M., Rege cambrin, Giovanna, Martino, Bruno, Abruzzese, Elisabetta, Albano, Francesco, Stagno, Fabio, Luciano, Luigia, D'Adda, Mariella, Bocchia, Monica, Cavazzini, Francesco, Tiribelli, Mario, Lunghi, Monia, Pia Falcone, Antonietta, Musolino, Caterina, Levato, Luciano, Venturi, Claudia, Soverini, Simona, Cavo, Michele, Alimena, Giuliana, Pane, Fabrizio, Martinelli, Giovanni, Saglio, Giuseppe, Rosti, Gianantonio, Baccarani, Michele, Gugliotta, Gabriele, Castagnetti, Fausto, Breccia, Massimo, Gozzini, Antonella, Usala, Emilio, Carella, Angelo M., Rege Cambrin, Giovanna, Martino, Bruno, Abruzzese, Elisabetta, Albano, Francesco, Stagno, Fabio, Luciano, Luigia, D'Adda, Mariella, Bocchia, Monica, Cavazzini, Francesco, Tiribelli, Mario, Lunghi, Monia, Pia Falcone, Antonietta, Musolino, Caterina, Levato, Luciano, Venturi, Claudia, Soverini, Simona, Cavo, Michele, Alimena, Giuliana, Pane, Fabrizio, Martinelli, Giovanni, Saglio, Giuseppe, Rosti, Gianantonio, Baccarani, Michele, and Rege-Cambrin, Giovanna
- Subjects
Myeloid ,Adult ,Male ,Adolescent ,Aged ,Aged, 80 and over ,Cardiovascular Diseases ,Drug Administration Schedule ,Female ,Humans ,Imatinib Mesylate ,Leukemia, Myeloid, Chronic-Phase ,Middle Aged ,Protein Kinase Inhibitors ,Pyrimidines ,Survival Analysis ,Survival Rate ,Treatment Outcome ,Young Adult ,Hematology ,Socio-culturale ,hemic and lymphatic diseases ,80 and over ,Leukemia ,Medicine (all) ,Hematology, nilotimib, chronic myeloid leukemia ,respiratory tract diseases ,Chronic-Phase - Abstract
The introduction of second-generation tyrosine-kinase inhibitors (TKIs) has generated a lively debate on the choice of first-line TKI in chronic phase, chronic myeloid leukemia (CML). Despite the TKIs have different efficacy and toxicity profiles, the planned use of two TKIs has never been investigated. We report on a phase 2 study that was designed to evaluate efficacy and safety of a treatment alternating nilotinib and imatinib, in newly diagnosed BCR-ABL1 positive, chronic phase, CML patients. One hundred twenty-three patients were enrolled. Median age was 56 years. The probabilities of achieving a complete cytogenetic response, a major molecular response, and a deep molecular response (MR 4.0) by 2 years were 93%, 87%, and 61%, respectively. The 5-year overall survival and progression-free survival were 89%. Response rates and survival are in the range of those reported with nilotinib alone. Moreover, we observed a relatively low rate of cardiovascular adverse events (5%). These data show that the different efficacy and toxicity profiles of TKIs could be favorably exploited by alternating their use. Am. J. Hematol. 91:617-622, 2016. © 2016 Wiley Periodicals, Inc.
- Published
- 2016
3. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy following autologous hematopoietic stem-cell transplantation in patients with newly diagnosed multiple myeloma
- Author
-
Cavo, Michele, Pantani, Lucia, Petrucci, Maria Teresa, Patriarca, Francesca, Zamagni, Elena, Donnarumma, Daniela, Crippa, Claudia, Boccadoro, Mario, Perrone, Giulia, Falcone, Antonietta, Nozzoli, Chiara, Zambello, Renato, Masini, Luciano, Furlan, Anna, Brioli, Annamaria, Derudas, Daniele, Ballanti, Stelvio, Dessanti, Maria Laura, De Stefano, Valerio, Carella, Angelo Michele, Marcatti, Magda, Nozza, Andrea, Ferrara, Felicetto, Callea, Vincenzo, Califano, Catello, Pezzi, Annalisa, Baraldi, Anna, Grasso, Mariella, Musto, Pellegrino, Palumbo, Antonio COLLABORATORI: Tosi, P, Motta, Mr, Rizzi, S, Fanin, R, Buttignol, S, Foà, R, Levi, A, Calabrese, E, Rambaldi, A, Galli, M, Rossi, G, Ferrari, S, Bringhen, S, Leoni, P, Offidani, M, Polloni, C, Corradini, P, Montefusco, V, Torelli, G, Narni, Franco, Fioritoni, G, Spadano, A, Cortelazzo, S, Pescosta, N, Billio, A, Lambertenghi Deliliers, G, Baldini, L, Onida, F, Annaloro, C, La Nasa, G, Ledda, A, Zaccaria, A, Cellini, C, De Fabritiis, P, Caravita, T, Siniscalchi, A, Cascavilla, N, Bosi, A, Semenzato, G, Gugliotta, L, Merli, F, Gherlinzoni, F, Angelucci, E, Martelli, M, Petti, Mc, Pisani, F, Leone, G, Rossi, E, Za, T, Fianchi, L, Catania, G, Spriano, M, Ciceri, F, Peccatori, J, Girlanda, S, Santoro, A, Castagna, L, Palmieri, S, Nobile, F, D'Arco, Am, Levis, A, Primon, V, Tamiazzo, S, Guardigni, L, Pasini, S, Gallamini, A, Pietrantuono, G, Martorelli, Mc, Fattori, P, Pasquini, E, Galieni, P, Ruggieri, M, Morandi, S, Tajana, M, Amadori, D, Ronconi, S, Cangini, D, Ceccolini, M, Gobbi, M, Ballerini, F, Pane, F, Catalano, L, Cangialosi, C, Vallisa, D, Lazzaro, A, Paladini, G, De Sabbata, G, Mozzana, R, Ciambelli, F, Pinotti, G, Rodeghiero, F, Elice, F, Cantore, N, Volpe, S, Pavone, V, Mele, A, Pogliani, E, Rossini, F, Liberati, A, Majolino, I, De Rosa, L, Amadori, S, Rizzo, M, Lauria, F, Gozzetti, A, Aglietta, M, Capaldi, A, Quarta, G, Mele, G, Storti, S, Fraticelli, V, Morabito, F, Gentile, C, Capalbo, S, Gianni, A, Magni, M, Mettivier, V, Nunziata, G, Rizzoli, V, Giuliani, N, Crugnola, M, Bernasconi, C, Fregoni, V, Visani, G, Olivieri, A, Pizzuti, M, La Verde, G, Moscetti, A, Avvisati, G, Tirindelli, M, Longinotti, M, Podda, L, Gallo, E, Pregno, P, Dammacco, F, Perosa, F, Russo, D, Roccaro, A, Bacigalupo, A, Dominietto, A, Musolino, C, Quartarone, E., Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A., Cavo, Michele, Pantani, Lucia, Petrucci, Maria Teresa, Patriarca, Francesca, Zamagni, Elena, Donnarumma, Daniela, Crippa, Claudia, Boccadoro, Mario, Perrone, Giulia, Falcone, Antonietta, Nozzoli, Chiara, Zambello, Renato, Masini, Luciano, Furlan, Anna, Brioli, Annamaria, Derudas, Daniele, Ballanti, Stelvio, Dessanti, Maria Laura, De Stefano, Valerio, Carella, Angelo Michele, Marcatti, Magda, Nozza, Andrea, Ferrara, Felicetto, Callea, Vincenzo, Califano, Catello, Pezzi, Annalisa, Baraldi, Anna, Grasso, Mariella, Musto, Pellegrino, Palumbo, Antonio, Cavo, M, Pantani, L, Petrucci, M, Patriarca, F, Zamagni, E, Donnarumma, D, Crippa, C, Boccadoro, M, Perrone, G, Falcone, A, Nozzoli, C, Zambello, R, Masini, L, Furlan, A, Brioli, A, Derudas, D, Ballanti, S, Dessanti, M, De Stefano, V, Carella, A, Marcatti, M, Nozza, A, Ferrara, F, Callea, V, Califano, C, Pezzi, A, Baraldi, A, Grasso, M, Musto, P, Palumbo, A, Tosi, P, Motta, M, Rizzi, S, Fanin, R, Buttignol, S, Foà, R, Levi, A, Calabrese, E, Rambaldi, A, Galli, M, Rossi, G, Ferrari, S, Bringhen, S, Leoni, P, Offidani, M, Polloni, C, Corradini, P, Montefusco, V, Torelli, G, Narni, F, Fioritoni, G, Spadano, A, Cortelazzo, S, Pescosta, N, Billio, A, Lambertenghi Deliliers, G, Baldini, L, Onida, F, Annaloro, C, La Nasa, G, Ledda, A, Zaccaria, A, Cellini, C, De Fabritiis, P, Caravita, T, Siniscalchi, A, Cascavilla, N, Bosi, A, Semenzato, G, Gugliotta, L, Merli, F, Gherlinzoni, F, Angelucci, E, Martelli, M, Petti, M, Pisani, F, Leone, G, Rossi, E, Za, T, Fianchi, L, Catania, G, Spriano, M, Ciceri, F, Peccatori, J, Girlanda, S, Santoro, A, Castagna, L, Palmieri, S, Nobile, F, D'Arco, A, Levis, A, Primon, V, Tamiazzo, S, Guardigni, L, Pasini, S, Gallamini, A, Pietrantuono, G, Martorelli, M, Fattori, P, Pasquini, E, Galieni, P, Ruggieri, M, Morandi, S, Tajana, M, Amadori, D, Ronconi, S, Cangini, D, Ceccolini, M, Gobbi, M, Ballerini, F, Pane, F, Catalano, L, Cangialosi, C, Vallisa, D, Lazzaro, A, Paladini, G, De Sabbata, G, Mozzana, R, Ciambelli, F, Pinotti, G, Rodeghiero, F, Elice, F, Cantore, N, Volpe, S, Pavone, V, Mele, A, Pogliani, E, Rossini, F, Liberati, A, Majolino, I, De Rosa, L, Amadori, S, Rizzo, M, Lauria, F, Gozzetti, A, Aglietta, M, Capaldi, A, Quarta, G, Mele, G, Storti, S, Fraticelli, V, Morabito, F, Gentile, C, Capalbo, S, Gianni, A, Magni, M, Mettivier, V, Nunziata, G, Rizzoli, V, Giuliani, N, Crugnola, M, Bernasconi, C, Fregoni, V, Visani, G, Olivieri, A, Pizzuti, M, La Verde, G, Moscetti, A, Avvisati, G, Tirindelli, M, Longinotti, M, Podda, L, Gallo, E, Pregno, P, Dammacco, F, Perosa, F, Russo, D, Roccaro, A, Bacigalupo, A, Dominietto, A, Musolino, C, and Quartarone, E
- Subjects
Male ,Boronic Acid ,medicine.medical_treatment ,PLUS DEXAMETHASONE ,Phases of clinical research ,Kaplan-Meier Estimate ,Hematopoietic stem cell transplantation ,Biochemistry ,Antineoplastic Agent ,Bortezomib-thalidomide-dexamethasone ,Bortezomib ,Immunosuppressive Agent ,Autologous stem-cell transplantation ,MULTIPLE MYELOMA ,Antineoplastic Combined Chemotherapy Protocols ,thalidomide-dexamethasone ,Multiple myeloma ,RANDOMIZED PHASE-3 ,LENALIDOMIDE ,STEM CELL TRANSPLANTATION ,Hematopoietic Stem Cell Transplantation ,PHASE-III TRIAL ,Hematology ,Middle Aged ,CHEMOTHERAPY ,Prognosis ,Boronic Acids ,Combined Modality Therapy ,Thalidomide ,Transplantation, Autologou ,Pyrazines ,HIGH-DOSE MELPHALAN ,INDUCTION TREATMENT ,Female ,Autologous ,Immunosuppressive Agents ,Pyrazine ,Human ,medicine.drug ,MAINTENANCE THERAPY ,medicine.medical_specialty ,DOXORUBICIN ,Antineoplastic Agents, Hormonal ,Prognosi ,Immunology ,Urology ,Antineoplastic Agents ,dexamethasone ,Transplantation, Autologous ,Disease-Free Survival ,Dexamethasone ,Humans ,Multiple Myeloma ,Cell Biology ,medicine ,Autologous transplantation ,METAANALYSIS ,Transplantation ,Antineoplastic Combined Chemotherapy Protocol ,Hormonal ,business.industry ,medicine.disease ,Surgery ,business ,Settore MED/15 - Malattie del Sangue - Abstract
In a randomized, phase 3 study, superior complete/near-complete response (CR/nCR) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autologous stem cell transplantation for newly diagnosed myeloma patients (intention-to-treat analysis; VTD, n = 236; TD, n = 238). This per-protocol analysis (VTD, n = 160; TD, n = 161) specifically assessed the efficacy and safety of consolidation with VTD or TD. Before starting consolidation, CR/nCR rates were not significantly different in the VTD (63.1%) and TD arms (54.7%). After consolidation, CR (60.6% vs 46.6%) and CR/nCR (73.1% vs 60.9%) rates were significantly higher for VTD-treated versus TD-treated patients. VTD consolidation significantly increased CR and CR/nCR rates, but TD did not (McNemar test). With a median follow-up of 30.4 months from start of consolidation, 3-year progression-free survival was significantly longer for the VTD group (60% vs 48% for TD). Grade 2 or 3 peripheral neuropathy (8.1% vs 2.4%) was more frequent with VTD (grade 3, 0.6%) versus TD consolidation. The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation. VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients randomly assigned to the VTD arm of the study. The study is registered at www.clinicaltrials.gov as #NCT01134484.
- Published
- 2012
4. Carfilzomib combined with lenalidomide and dexamethasone (KRd) as salvage therapy for multiple myeloma patients: italian, multicenter, retrospective clinical experience with 600 cases outside of controlled clinical trials
- Author
-
Enrica Antonia Martino, Concetta Conticello, Elena Zamagni, Vincenzo Pavone, Salvatore Palmieri, Maurizio Musso, Paola Tacchetti, Anna Mele, Lucio Catalano, Ernesto Vigna, Antonella Bruzzese, Francesco Mendicino, Cirino Botta, Iolanda Donatella Vincelli, Giuliana Farina, Marialucia Barone, Clotilde Cangialosi, Katia Mancuso, Ilaria Rizziello, Serena Rocchi, Antonietta Pia Falcone, Giuseppe Mele, Giovanni Reddiconto, Bruno Garibaldi, Enrico Iaccino, Giovanni Tripepi, Barbara Gamberi, Francesco Di Raimondo, Pellegrino Musto, Antonino Neri, Michele Cavo, Fortunato Morabito, Massimo Gentile, Martino, Enrica Antonia, Conticello, Concetta, Zamagni, Elena, Pavone, Vincenzo, Palmieri, Salvatore, Musso, Maurizio, Tacchetti, Paola, Mele, Anna, Catalano, Lucio, Vigna, Ernesto, Bruzzese, Antonella, Mendicino, Francesco, Botta, Cirino, Vincelli, Iolanda Donatella, Farina, Giuliana, Barone, Marialucia, Cangialosi, Clotilde, Mancuso, Katia, Rizziello, Ilaria, Rocchi, Serena, Falcone, Antonietta Pia, Mele, Giuseppe, Reddiconto, Giovanni, Garibaldi, Bruno, Iaccino, Enrico, Tripepi, Giovanni, Gamberi, Barbara, Di Raimondo, Francesco, Musto, Pellegrino, Neri, Antonino, Cavo, Michele, Morabito, Fortunato, and Gentile, Massimo
- Subjects
Salvage Therapy ,Cancer Research ,Oncology ,Humans ,Hematology ,General Medicine ,KRd regimen, multiple myeloma, salvage therapy ,Multiple Myeloma ,Lenalidomide ,Dexamethasone ,Retrospective Studies - Abstract
In combination with lenalidomide and dexamethasone (KRd), Carfilzomib has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) on ASPIRE trial. Efficacy and safety of the triplet are still the object of investigation by many groups to confirm ASPIRE results in the setting of RRMM treated in real-life who don't meet trial restrictive inclusion criteria. Therefore, we report a retrospective multicenter analysis of 600 RRMM patients treated with KRd between December 2015 and December 2018. The median age was 64 years (range 33-85), and the median number of previous therapies was two (range 1-11). After a median of 11 KRd cycles, the overall response rate was 79.9%. The median progression-free survival (PFS) was 22 months, and the 2-year probability of PFS was 47.6%. Creatinine clearance30 ml/min,1 line of previous therapy, and high-risk FISH were all associated with a poor prognosis in multivariate analysis. The median overall survival (OS) was 34.8 months; the 2-year probability of OS was 63.5%. At multivariate analysis, creatinine clearance30 ml/min,1 line of previous therapy, and high-risk FISH were significantly associated with poor prognosis. After a median follow-up of 16 months (range 1-50), 259 withdrew from therapy. The main discontinuation reason was progressive disease (81.8%). Seventy-four patients (12.3%) discontinued therapy for toxicity. The most frequent side effects were hematological (anemia 49.3%, neutropenia 42.7%, thrombocytopenia 42.5%) and cardiovascular (hypertension 14.5%, heart failure 2.5%, arrhythmias 3.6%). Our study confirms the safety and efficacy of KRd in the real-life setting of RRMM patients and encourages its use in clinical practice.
- Published
- 2022
5. Is re-challenge still an option as salvage therapy in multiple myeloma? The case of REal-life BOrtezomib re-Use as secoND treatment for relapsed patients exposed frontline to bortezomib-based therapies (the REBOUND Study)
- Author
-
Nicola Di Renzo, Concetta Conticello, Lucia Mastrullo, Giovanni Reddiconto, Alberto Fragasso, Daniele Scapicchio, Roberto Ria, Maria Teresa Petrucci, Gioacchino Marziano, Nicola Cascavilla, Alfredo Gagliardi, Vittorio Simeon, Silvia Mangiacavalli, Alessandro Corso, Giovanni D'Arena, Francesco Di Raimondo, Giovanna Mansueto, Lucio Catalano, Antonietta Falcone, Pellegrino Musto, Laura Cesini, Tommaso Caravita, Sara Bringhen, Giuseppe Pietrantuono, Oreste Villani, Dalila Salvatore, Mariella Genuardi, Mario Boccadoro, Musto, Pellegrino, Simeon, Vittorio, Cascavilla, Nicola, Falcone, Antonietta, Petrucci, Maria Teresa, Cesini, Laura, Di Raimondo, Francesco, Conticello, Concetta, Ria, Roberto, Catalano, Lucio, Salvatore, Dalila, Mastrullo, Lucia, Gagliardi, Alfredo, Villani, Oreste, Pietrantuono, Giuseppe, D'Arena, Giovanni, Mansueto, Giovanna, Bringhen, Sara, Genuardi, Mariella, Di Renzo, Nicola, Reddiconto, Giovanni, Fragasso, Alberto, Caravita, Tommaso, Scapicchio, Daniele, Marziano, Gioacchino, Boccadoro, Mario, Mangiacavalli, Silvia, and Corso, Alessandro
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Salvage therapy ,Myeloma ,First relapse ,Disease-Free Survival ,Bortezomib ,Re-treatment ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Internal medicine ,medicine ,Humans ,Survival rate ,Multiple myeloma ,Aged ,Retrospective Studies ,Salvage Therapy ,Hematology ,business.industry ,Female ,Follow-Up Studies ,Middle Aged ,Multiple Myeloma ,Survival Rate ,Retrospective cohort study ,General Medicine ,medicine.disease ,030220 oncology & carcinogenesis ,Observational study ,business ,030215 immunology ,medicine.drug - Abstract
Therapeutic re-challenge is currently a debated issue in the field of multiple myeloma (MM), given the recent availability of several new drugs and combinations. However, very few specific evidences are available about bortezomib re-use at first relapse. This multicenter, observational, retrospective study enrolled 134 MM patients with significant response after bortezomib-based frontline regimens and who had received a first salvage treatment containing bortezomib at relapse. The overall response rate was 71%, including 40% partial responses, 24% very good partial responses, and 7% complete responses. Re-treatment was well-tolerated, with no significant new or unexpected toxicities observed. The median duration of second progression-free survival (PFS) was 15 months, while median PFS2 was 55 months. With a median follow-up of 56 months, overall survival was 94 months for the entire series, without significant differences between patients undergoing or not undergoing transplant procedures. This real-life survey indicates that re-treatment including bortezomib as a first salvage therapy could be still considered in MM patients achieving durable response after initial exposure to bortezomib.
- Published
- 2018
6. Whole-exome sequencing of primary plasma cell leukemia discloses heterogeneous mutational patterns
- Author
-
Antonietta Falcone, Antonino Neri, Sonia Fabris, Alessandro Pietrelli, Francesco Di Raimondo, Ingrid Cifola, Vittorio Simeon, Maria Teresa Petrucci, Tommaso Caravita, Antonio Palumbo, K. Todoerti, Gianluca De Bellis, Eva Pinatel, Pellegrino Musto, Fortunato Morabito, Massimo Offidani, Laura Mosca, Eleonora Mangano, Cristina Battaglia, Marta Lionetti, Cifola, Ingrid, Lionetti, Marta, Pinatel, Eva, Todoerti, Katia, Mangano, Eleonora, Pietrelli, Alessandro, Fabris, Sonia, Mosca, Laura, Simeon, Vittorio, Petrucci, Maria Teresa, Morabito, Fortunato, Offidani, Massimo, Di Raimondo, Francesco, Falcone, Antonietta, Caravita, Tommaso, Battaglia, Cristina, De Bellis, Gianluca, Palumbo, Antonio, Musto, Pellegrino, and Neri, Antonino
- Subjects
medicine.medical_specialty ,DNA Mutational Analysis ,Plasma cell dyscrasia ,Leukemia, Plasma Cell ,03 medical and health sciences ,0302 clinical medicine ,Copy Number Alteration ,Internal medicine ,plasma cell leukemia ,Medicine ,Cluster Analysis ,Humans ,Exome ,whole-exome sequencing ,Exome sequencing ,030304 developmental biology ,Genome stability ,Genetics ,RNA metabolism ,Plasma cell leukemia ,0303 health sciences ,Hematology ,business.industry ,medicine.disease ,mutations ,3. Good health ,multiple myeloma ,Oncology ,Research council ,030220 oncology & carcinogenesis ,mutation ,business ,Research Paper - Abstract
// Ingrid Cifola 1, * , Marta Lionetti 2, 3, * , Eva Pinatel 1 , Katia Todoerti 4 , Eleonora Mangano 1 , Alessandro Pietrelli 1 , Sonia Fabris 2, 3 , Laura Mosca 2, 3 , Vittorio Simeon 4 , Maria Teresa Petrucci 5 , Fortunato Morabito 6 , Massimo Offidani 7 , Francesco Di Raimondo 8 , Antonietta Falcone 9 , Tommaso Caravita 10 , Cristina Battaglia 1, 11 , Gianluca De Bellis 1 , Antonio Palumbo 12 , Pellegrino Musto 13 , Antonino Neri 2, 3 1 Institute for Biomedical Technologies, National Research Council, Milan, Italy 2 Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy 3 Hematology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy 4 Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture (PZ), Italy 5 Hematology, Department of Cellular Biotechnologies and Hematology, La Sapienza University, Rome, Italy 6 Hematology Unit, Azienda Ospedaliera di Cosenza, Cosenza, Italy 7 Hematologic Clinic, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy 8 Department of Biomedical Sciences, Division of Hematology, Ospedale Ferrarotto, University of Catania, Catania, Italy 9 Hematology Unit, IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, Italy 10 Department of Hematology, Ospedale S. Eugenio, Tor Vergata University, Rome, Italy 11 Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy 12 Division of Hematology, University of Torino, A.O.U. San Giovanni Battista, Torino, Italy 13 Scientific Direction, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture (PZ), Italy * These authors have contributed equally to this work Correspondence to: Antonino Neri, e-mail: antonino.neri@unimi.it Ingrid Cifola, e-mail: ingrid.cifola@itb.cnr.it Keywords: whole-exome sequencing, plasma cell leukemia, multiple myeloma, mutations Received: April 29, 2015 Accepted: May 11, 2015 Published: May 25, 2015 ABSTRACT Primary plasma cell leukemia (pPCL) is a rare and aggressive form of plasma cell dyscrasia and may represent a valid model for high-risk multiple myeloma (MM). To provide novel information concerning the mutational profile of this disease, we performed the whole-exome sequencing of a prospective series of 12 pPCL cases included in a Phase II multicenter clinical trial and previously characterized at clinical and molecular levels. We identified 1, 928 coding somatic non-silent variants on 1, 643 genes, with a mean of 166 variants per sample, and only few variants and genes recurrent in two or more samples. An excess of C > T transitions and the presence of two main mutational signatures (related to APOBEC over-activity and aging) occurring in different translocation groups were observed. We identified 14 candidate cancer driver genes, mainly involved in cell-matrix adhesion, cell cycle, genome stability, RNA metabolism and protein folding. Furthermore, integration of mutation data with copy number alteration profiles evidenced biallelically disrupted genes with potential tumor suppressor functions. Globally, cadherin/Wnt signaling, extracellular matrix and cell cycle checkpoint resulted the most affected functional pathways. Sequencing results were finally combined with gene expression data to better elucidate the biological relevance of mutated genes. This study represents the first whole-exome sequencing screen of pPCL and evidenced a remarkable genetic heterogeneity of mutational patterns. This may provide a contribution to the comprehension of the pathogenetic mechanisms associated with this aggressive form of PC dyscrasia and potentially with high-risk MM.
Catalog
Books, media, physical & digital resources
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.