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141 results on '"Bonfiglio, Silvia"'

1. Genetic determinants of type 1 diabetes in individuals with weak evidence of islet autoimmunity at disease onset

Author

Carrera, Paola, Marzinotto, Ilaria, Bonfanti, Riccardo, Massimino, Luca, Calzavara, Silvia, Favellato, Μariagrazia, Jofra, Tatiana, De Giglio, Valeria, Bonura, Clara, Stabilini, Angela, Favalli, Valeria, Bondesan, Simone, Cicalese, Maria Pia, Laurenzi, Andrea, Caretto, Amelia, Frontino, Giulio, Rigamonti, Andrea, Molinari, Chiara, Scavini, Marina, Sandullo, Federica, Zapparoli, Ettore, Caridi, Nicoletta, Bonfiglio, Silvia, Castorani, Valeria, Ungaro, Federica, Petrelli, Alessandra, Barera, Graziano, Aiuti, Alessandro, Bosi, Emanuele, Battaglia, Manuela, Piemonti, Lorenzo, Lampasona, Vito, and Fousteri, Georgia

Published
2023
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2. Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY

Author

Mansouri, Larry, Thorvaldsdottir, Birna, Sutton, Lesley-Ann, Karakatsoulis, Georgios, Meggendorfer, Manja, Parker, Helen, Nadeu, Ferran, Brieghel, Christian, Laidou, Stamatia, Moia, Riccardo, Rossi, Davide, Catherwood, Mark, Kotaskova, Jana, Delgado, Julio, Rodríguez-Vicente, Ana E., Benito, Rocío, Rigolin, Gian Matteo, Bonfiglio, Silvia, Scarfo, Lydia, Mattsson, Mattias, Davis, Zadie, Gogia, Ajay, Rani, Lata, Baliakas, Panagiotis, Foroughi-Asl, Hassan, Jylhä, Cecilia, Skaftason, Aron, Rapado, Inmaculada, Miras, Fatima, Martinez-Lopez, Joaquín, de la Serna, Javier, Rivas, Jesús María Hernández, Thornton, Patrick, Larráyoz, María José, Calasanz, María José, Fésüs, Viktória, Mátrai, Zoltán, Bödör, Csaba, Smedby, Karin E., Espinet, Blanca, Puiggros, Anna, Gupta, Ritu, Bullinger, Lars, Bosch, Francesc, Tazón-Vega, Bárbara, Baran-Marszak, Fanny, Oscier, David, Nguyen-Khac, Florence, Zenz, Thorsten, Terol, Maria Jose, Cuneo, Antonio, Hernández-Sánchez, María, Pospisilova, Sarka, Mills, Ken, Gaidano, Gianluca, Niemann, Carsten U., Campo, Elias, Strefford, Jonathan C., Ghia, Paolo, Stamatopoulos, Kostas, and Rosenquist, Richard

Published
2023
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3. BTK and PLCG2 remain unmutated in one-third of patients with CLL relapsing on ibrutinib

Author

Bonfiglio, Silvia, Sutton, Lesley-Ann, Ljungström, Viktor, Capasso, Antonella, Pandzic, Tatjana, Weström, Simone, Foroughi-Asl, Hassan, Skaftason, Aron, Gellerbring, Anna, Lyander, Anna, Gandini, Francesca, Gaidano, Gianluca, Trentin, Livio, Bonello, Lisa, Reda, Gianluigi, Bödör, Csaba, Stavroyianni, Niki, Tam, Constantine S., Marasca, Roberto, Forconi, Francesco, Panayiotidis, Panayiotis, Ringshausen, Ingo, Jaksic, Ozren, Frustaci, Anna Maria, Iyengar, Sunil, Coscia, Marta, Mulligan, Stephen P., Ysebaert, Loïc, Strugov, Vladimir, Pavlovsky, Carolina, Walewska, Renata, Österborg, Anders, Cortese, Diego, Ranghetti, Pamela, Baliakas, Panagiotis, Stamatopoulos, Kostas, Scarfò, Lydia, Rosenquist, Richard, and Ghia, Paolo

Published
2023
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4. High surface IgM levels associate with shorter response to ibrutinib and BTK bypass in patients with CLL

Author

Chiodin, Giorgia, Drennan, Samantha, Martino, Enrica A., Ondrisova, Laura, Henderson, Isla, del Rio, Luis, Tracy, Ian, D'Avola, Annalisa, Parker, Helen, Bonfiglio, Silvia, Scarfò, Lydia, Sutton, Lesley-Ann, Strefford, Jonathan C., Forster, Jade, Brake, Oliver, Potter, Kathleen N., Sale, Benjamin, Lanham, Stuart, Mraz, Marek, Ghia, Paolo, Stevenson, Freda K., and Forconi, Francesco

Published
2022
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5. Radiation-Related Deregulation of TUBB3 and BRCA1/2 and Risk of Secondary Lung Cancer in Women With Breast Cancer

Author

Coco, Simona, Boccardo, Simona, Mora, Marco, Fontana, Vincenzo, Vanni, Irene, Genova, Carlo, Alama, Angela, Salvi, Sandra, Dal Bello, Maria Giovanna, Bonfiglio, Silvia, Rijavec, Erika, Sini, Claudio, Barletta, Giulia, Biello, Federica, Carli, Franca, Cavalieri, Zita, Burrafato, Giovanni, Longo, Luca, Ballestrero, Alberto, and Grossi, Francesco

Published
2021
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6. Correction: Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY

Author

Mansouri, Larry, Thorvaldsdottir, Birna, Sutton, Lesley-Ann, Karakatsoulis, Georgios, Meggendorfer, Manja, Parker, Helen, Nadeu, Ferran, Brieghel, Christian, Laidou, Stamatia, Moia, Riccardo, Rossi, Davide, Catherwood, Mark, Kotaskova, Jana, Delgado, Julio, Rodríguez-Vicente, Ana E., Benito, Rocío, Rigolin, Gian Matteo, Bonfiglio, Silvia, Scarfo, Lydia, Mattsson, Mattias, Davis, Zadie, Gogia, Ajay, Rani, Lata, Baliakas, Panagiotis, Foroughi-Asl, Hassan, Jylhä, Cecilia, Skaftason, Aron, Rapado, Inmaculada, Miras, Fatima, Martinez-Lopez, Joaquín, de la Serna, Javier, Rivas, Jesús María Hernández, Thornton, Patrick, Larráyoz, María José, Calasanz, María José, Fésüs, Viktória, Mátrai, Zoltán, Bödör, Csaba, Smedby, Karin E., Espinet, Blanca, Puiggros, Anna, Gupta, Ritu, Bullinger, Lars, Bosch, Francesc, Tazón-Vega, Bárbara, Baran-Marszak, Fanny, Oscier, David, Nguyen-Khac, Florence, Zenz, Thorsten, Terol, Maria Jose, Cuneo, Antonio, Hernández-Sánchez, María, Pospisilova, Sarka, Mills, Ken, Gaidano, Gianluca, Niemann, Carsten U., Campo, Elias, Strefford, Jonathan C., Ghia, Paolo, Stamatopoulos, Kostas, and Rosenquist, Richard

Published
2023
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7. Supplementary Materials and methods from Preexisting Immunity Drives the Response to Neoadjuvant Chemotherapy in Esophageal Adenocarcinoma

Author

Arbore, Giuseppina, primary, Albarello, Luca, primary, Bucci, Gabriele, primary, Punta, Marco, primary, Cossu, Andrea, primary, Fanti, Lorella, primary, Maurizio, Aurora, primary, Di Mauro, Francesco, primary, Bilello, Vito, primary, Arrigoni, Gianluigi, primary, Bonfiglio, Silvia, primary, Biancolini, Donatella, primary, Puccetti, Francesco, primary, Elmore, Ugo, primary, Vago, Luca, primary, Cascinu, Stefano, primary, Tonon, Giovanni, primary, Rosati, Riccardo, primary, Casorati, Giulia, primary, and Dellabona, Paolo, primary

Published
2023
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8. Data from Preexisting Immunity Drives the Response to Neoadjuvant Chemotherapy in Esophageal Adenocarcinoma

Author

Arbore, Giuseppina, primary, Albarello, Luca, primary, Bucci, Gabriele, primary, Punta, Marco, primary, Cossu, Andrea, primary, Fanti, Lorella, primary, Maurizio, Aurora, primary, Di Mauro, Francesco, primary, Bilello, Vito, primary, Arrigoni, Gianluigi, primary, Bonfiglio, Silvia, primary, Biancolini, Donatella, primary, Puccetti, Francesco, primary, Elmore, Ugo, primary, Vago, Luca, primary, Cascinu, Stefano, primary, Tonon, Giovanni, primary, Rosati, Riccardo, primary, Casorati, Giulia, primary, and Dellabona, Paolo, primary

Published
2023
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9. Supplementary Tables from Preexisting Immunity Drives the Response to Neoadjuvant Chemotherapy in Esophageal Adenocarcinoma

Author

Arbore, Giuseppina, primary, Albarello, Luca, primary, Bucci, Gabriele, primary, Punta, Marco, primary, Cossu, Andrea, primary, Fanti, Lorella, primary, Maurizio, Aurora, primary, Di Mauro, Francesco, primary, Bilello, Vito, primary, Arrigoni, Gianluigi, primary, Bonfiglio, Silvia, primary, Biancolini, Donatella, primary, Puccetti, Francesco, primary, Elmore, Ugo, primary, Vago, Luca, primary, Cascinu, Stefano, primary, Tonon, Giovanni, primary, Rosati, Riccardo, primary, Casorati, Giulia, primary, and Dellabona, Paolo, primary

Published
2023
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10. Supplementary Figures from Preexisting Immunity Drives the Response to Neoadjuvant Chemotherapy in Esophageal Adenocarcinoma

Author

Arbore, Giuseppina, primary, Albarello, Luca, primary, Bucci, Gabriele, primary, Punta, Marco, primary, Cossu, Andrea, primary, Fanti, Lorella, primary, Maurizio, Aurora, primary, Di Mauro, Francesco, primary, Bilello, Vito, primary, Arrigoni, Gianluigi, primary, Bonfiglio, Silvia, primary, Biancolini, Donatella, primary, Puccetti, Francesco, primary, Elmore, Ugo, primary, Vago, Luca, primary, Cascinu, Stefano, primary, Tonon, Giovanni, primary, Rosati, Riccardo, primary, Casorati, Giulia, primary, and Dellabona, Paolo, primary

Published
2023
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11. Abstract 902: Harnessing CD39 for the treatment of colorectal cancer and liver metastases by engineered T cells

Author

Potenza, Alessia, primary, Balestrieri, Chiara, additional, Albarello, Luca, additional, Pedica, Federica, additional, Spiga, Martina, additional, Manfredi, Francesco, additional, Cianciotti, Beatrice C., additional, De Lalla, Claudia, additional, Stasi, Lorena, additional, Tassi, Elena, additional, Bonfiglio, Silvia, additional, Scotti, Giulia M., additional, Redegalli, Miriam, additional, Biancolini, Donatella, additional, Abbati, Danilo, additional, Simeoni, Fabio, additional, Lazarevic, Dejan, additional, Elmore, Ugo, additional, Fiorentini, Guido, additional, Lullo, Giulia Di, additional, Casorati, Giulia, additional, Doglioni, Claudio, additional, Tonon, Giovanni, additional, Dellabona, Paolo, additional, Rosati, Riccardo, additional, Aldrighetti, Luca, additional, Ruggiero, Eliana, additional, and Bonini, Chiara, additional

Published
2023
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12. Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status:a study by ERIC in HARMONY

Author

Mansouri, Larry, Thorvaldsdottir, Birna, Sutton, Lesley Ann, Karakatsoulis, Georgios, Meggendorfer, Manja, Parker, Helen, Nadeu, Ferran, Brieghel, Christian, Laidou, Stamatia, Moia, Riccardo, Rossi, Davide, Catherwood, Mark, Kotaskova, Jana, Delgado, Julio, Rodríguez-Vicente, Ana E., Benito, Rocío, Rigolin, Gian Matteo, Bonfiglio, Silvia, Scarfo, Lydia, Mattsson, Mattias, Davis, Zadie, Gogia, Ajay, Rani, Lata, Baliakas, Panagiotis, Foroughi-Asl, Hassan, Jylhä, Cecilia, Skaftason, Aron, Rapado, Inmaculada, Miras, Fatima, Martinez-Lopez, Joaquín, de la Serna, Javier, Rivas, Jesús María Hernández, Thornton, Patrick, Larráyoz, María José, Calasanz, María José, Fésüs, Viktória, Mátrai, Zoltán, Bödör, Csaba, Smedby, Karin E., Espinet, Blanca, Puiggros, Anna, Gupta, Ritu, Bullinger, Lars, Bosch, Francesc, Tazón-Vega, Bárbara, Baran-Marszak, Fanny, Oscier, David, Nguyen-Khac, Florence, Zenz, Thorsten, Terol, Maria Jose, Cuneo, Antonio, Hernández-Sánchez, María, Pospisilova, Sarka, Mills, Ken, Gaidano, Gianluca, Niemann, Carsten U., Campo, Elias, Strefford, Jonathan C., Ghia, Paolo, Stamatopoulos, Kostas, Rosenquist, Richard, Mansouri, Larry, Thorvaldsdottir, Birna, Sutton, Lesley Ann, Karakatsoulis, Georgios, Meggendorfer, Manja, Parker, Helen, Nadeu, Ferran, Brieghel, Christian, Laidou, Stamatia, Moia, Riccardo, Rossi, Davide, Catherwood, Mark, Kotaskova, Jana, Delgado, Julio, Rodríguez-Vicente, Ana E., Benito, Rocío, Rigolin, Gian Matteo, Bonfiglio, Silvia, Scarfo, Lydia, Mattsson, Mattias, Davis, Zadie, Gogia, Ajay, Rani, Lata, Baliakas, Panagiotis, Foroughi-Asl, Hassan, Jylhä, Cecilia, Skaftason, Aron, Rapado, Inmaculada, Miras, Fatima, Martinez-Lopez, Joaquín, de la Serna, Javier, Rivas, Jesús María Hernández, Thornton, Patrick, Larráyoz, María José, Calasanz, María José, Fésüs, Viktória, Mátrai, Zoltán, Bödör, Csaba, Smedby, Karin E., Espinet, Blanca, Puiggros, Anna, Gupta, Ritu, Bullinger, Lars, Bosch, Francesc, Tazón-Vega, Bárbara, Baran-Marszak, Fanny, Oscier, David, Nguyen-Khac, Florence, Zenz, Thorsten, Terol, Maria Jose, Cuneo, Antonio, Hernández-Sánchez, María, Pospisilova, Sarka, Mills, Ken, Gaidano, Gianluca, Niemann, Carsten U., Campo, Elias, Strefford, Jonathan C., Ghia, Paolo, Stamatopoulos, Kostas, and Rosenquist, Richard

Abstract

Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3–9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management.

Published
2023

13. Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY

Author

Associazione Italiana per la Ricerca sul Cancro, Ministero della Salute, Fundación la Caixa, American Association for Cancer Research, European Hematology Association, Lady Tata Memorial Trust, European Association for Cancer Research, Instituto de Salud Carlos III, Ministry of Innovation and Technology (Hungary), Università degli Studi di Ferrara, Associazione Italiana Contro le Leucemie - Linfomi e Mieloma, Danish Cancer Society Research Center, Cancer Research UK, Swedish Cancer Society, Swedish Research Council, Knut and Alice Wallenberg Foundation, Lions Cancerforskningsfond, Mansouri, Larry, Thorvaldsdottir, Birna, Sutton, Lesley-Ann, Karakatsoulis, Georgios, Meggendorfer, Manja, Parker, Helen, Nadeu, Ferran, Brieghel, Christian, Laidou, Stamatia, Moia, Riccardo, Rossi, Davide, Catherwood, Mark, Kotaskova, Jana, Delgado, Julio, Rodríguez-Vicente, Ana Eugenia, Benito, Rocío, Rigolin, Gian Matteo, Bonfiglio, Silvia, Scarfo, Lydia, Mattsson, Mattias, Davis, Zadie, Gogia, Ajay, Rani, Lata, Baliakas, Panagiotis, Foroughi-Asl, Hassan, Jylhä, Cecilia, Skaftason, Aron, Rapado, Inmaculada, Mirás, Fátima, Martínez-López, Joaquín, Serna, Javier de la, De Las Rivas, Javier, Thornton, Patrick, Larráyoz, María José, Calasanz, Mª Jose, Fésüs, Viktória, Mátrai, Zoltán, Bödör, Csaba, Smedby, Karin E, Espinet, Blanca, Puiggros, Anna, Gupta, Ritu, Bullinger, Lars, Bosch, Francesc, Tazón‐Vega, Bárbara, Baran-Marszak, Fanny, Oscier, David, Nguyen-Khac, Florence, Zenz, Thorsten, Terol, María José, Cuneo, Antonio, Hernández-Sánchez, María, Pospisilova, Sarka, Mills, Ken, Gaidano, Gianluca, Niemann, Carsten U, Campo, Elías, Strefford, Jonathan C, Ghia, Paolo, Stamatopoulos, Kostas, Rosenquist, Richard, Associazione Italiana per la Ricerca sul Cancro, Ministero della Salute, Fundación la Caixa, American Association for Cancer Research, European Hematology Association, Lady Tata Memorial Trust, European Association for Cancer Research, Instituto de Salud Carlos III, Ministry of Innovation and Technology (Hungary), Università degli Studi di Ferrara, Associazione Italiana Contro le Leucemie - Linfomi e Mieloma, Danish Cancer Society Research Center, Cancer Research UK, Swedish Cancer Society, Swedish Research Council, Knut and Alice Wallenberg Foundation, Lions Cancerforskningsfond, Mansouri, Larry, Thorvaldsdottir, Birna, Sutton, Lesley-Ann, Karakatsoulis, Georgios, Meggendorfer, Manja, Parker, Helen, Nadeu, Ferran, Brieghel, Christian, Laidou, Stamatia, Moia, Riccardo, Rossi, Davide, Catherwood, Mark, Kotaskova, Jana, Delgado, Julio, Rodríguez-Vicente, Ana Eugenia, Benito, Rocío, Rigolin, Gian Matteo, Bonfiglio, Silvia, Scarfo, Lydia, Mattsson, Mattias, Davis, Zadie, Gogia, Ajay, Rani, Lata, Baliakas, Panagiotis, Foroughi-Asl, Hassan, Jylhä, Cecilia, Skaftason, Aron, Rapado, Inmaculada, Mirás, Fátima, Martínez-López, Joaquín, Serna, Javier de la, De Las Rivas, Javier, Thornton, Patrick, Larráyoz, María José, Calasanz, Mª Jose, Fésüs, Viktória, Mátrai, Zoltán, Bödör, Csaba, Smedby, Karin E, Espinet, Blanca, Puiggros, Anna, Gupta, Ritu, Bullinger, Lars, Bosch, Francesc, Tazón‐Vega, Bárbara, Baran-Marszak, Fanny, Oscier, David, Nguyen-Khac, Florence, Zenz, Thorsten, Terol, María José, Cuneo, Antonio, Hernández-Sánchez, María, Pospisilova, Sarka, Mills, Ken, Gaidano, Gianluca, Niemann, Carsten U, Campo, Elías, Strefford, Jonathan C, Ghia, Paolo, Stamatopoulos, Kostas, and Rosenquist, Richard

Abstract

Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3–9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management.

Published
2023

15. Revealing and harnessing CD39 for the treatment of colorectal cancer and liver metastases by engineered T cells.

Author

Potenza, Alessia, Balestrieri, Chiara, Spiga, Martina, Albarello, Luca, Pedica, Federica, Manfredi, Francesco, Claudia Cianciotti, Beatrice, De Lalla, Claudia, Botrugno, Oronza A., Faccani, Cristina, Stasi, Lorena, Tassi, Elena, Bonfiglio, Silvia, Scotti, Giulia Maria, Redegalli, Miriam, Biancolini, Donatella, Camisa, Barbara, Tiziano, Elena, Sirini, Camilla, and Casucci, Monica

Subjects
COLORECTAL liver metastasis, T cells, BLADDER cancer, MONONUCLEAR leukocytes, T-cell exhaustion, KILLER cells
Published
2023
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16. Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY

Author

Mansouri, Larry, primary, Thorvaldsdottir, Birna, additional, Sutton, Lesley-Ann, additional, Karakatsoulis, Georgios, additional, Meggendorfer, Manja, additional, Parker, Helen, additional, Nadeu, Ferran, additional, Brieghel, Christian, additional, Laidou, Stamatia, additional, Moia, Riccardo, additional, Rossi, Davide, additional, Catherwood, Mark, additional, Kotaskova, Jana, additional, Delgado, Julio, additional, Rodríguez-Vicente, Ana E., additional, Benito, Rocío, additional, Rigolin, Gian Matteo, additional, Bonfiglio, Silvia, additional, Scarfo, Lydia, additional, Mattsson, Mattias, additional, Davis, Zadie, additional, Gogia, Ajay, additional, Rani, Lata, additional, Baliakas, Panagiotis, additional, Foroughi-Asl, Hassan, additional, Jylhä, Cecilia, additional, Skaftason, Aron, additional, Rapado, Inmaculada, additional, Miras, Fatima, additional, Martinez-Lopez, Joaquín, additional, de la Serna, Javier, additional, Rivas, Jesús María Hernández, additional, Thornton, Patrick, additional, Larráyoz, María José, additional, Calasanz, María José, additional, Fésüs, Viktória, additional, Mátrai, Zoltán, additional, Bödör, Csaba, additional, Smedby, Karin E., additional, Espinet, Blanca, additional, Puiggros, Anna, additional, Gupta, Ritu, additional, Bullinger, Lars, additional, Bosch, Francesc, additional, Tazón-Vega, Bárbara, additional, Baran-Marszak, Fanny, additional, Oscier, David, additional, Nguyen-Khac, Florence, additional, Zenz, Thorsten, additional, Terol, Maria Jose, additional, Cuneo, Antonio, additional, Hernández-Sánchez, María, additional, Pospisilova, Sarka, additional, Mills, Ken, additional, Gaidano, Gianluca, additional, Niemann, Carsten U., additional, Campo, Elias, additional, Strefford, Jonathan C., additional, Ghia, Paolo, additional, Stamatopoulos, Kostas, additional, and Rosenquist, Richard, additional

Published
2022
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17. 268 Harnessing CD39 for the treatment of colorectal cancer and liver metastases by engineered T cells

Author

Potenza, Alessia, primary, Bonini, Chiara, additional, Balestrieri, Chiara, additional, Albarello, Luca, additional, Pedica, Federica, additional, Spiga, Martina, additional, Manfredi, Francesco, additional, Cianciotti, Beatrice, additional, Lalla, Claudia De, additional, Stasi, Lorena, additional, Tassi, Elena, additional, Bonfiglio, Silvia, additional, Scotti, Giulia, additional, Redegalli, Miriam, additional, Biancolini, Donatella, additional, Abbati, Danilo, additional, Simeoni, Fabio, additional, Lazarevic, Dejan, additional, Elmore, Ugo, additional, Fiorentini, Guido, additional, Lullo, Giulia Di, additional, Casorati, Giulia, additional, Dellabona, Paolo, additional, Doglioni, Claudio, additional, Tonon, Giovanni, additional, Rosati, Riccardo, additional, Aldrighetti, Luca, additional, and Ruggiero, Eliana, additional

Published
2022
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18. Prospective Validation of the Italian Alliance Against Cancer Lung Panel in Patients With Advanced Non–Small-Cell Lung Cancer

Author

Gregorc, Vanesa, Mazzarella, Luca, Lazzari, Chiara, Graziano, Paolo, Vigneri, Paolo, Genova, Carlo, Toschi, Luca, Ciliberto, Gennaro, Bonanno, Laura, Delmonte, Angelo, Bucci, Gabriele, Rossi, Antonio, Motta, Gianmarco, Coco, Simona, Marinello, Arianna, Buglioni, Simonetta, Cangi, Maria Giulia, Di Micco, Concetta, Bandiera, Alessandro, Bonfiglio, Silvia, Pecciarini, Lorenza, Guida, Alessandro, Ceol, Arnaud, Frige’, Gianmaria, De Maria, Ruggero, and Pelicci, Pier Giuseppe

Published
2021
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19. Different Prognostic Impact of Recurrent Gene Mutations in IGHV-Mutated and IGHV-Unmutated Chronic Lymphocytic Leukemia: A Retrospective, Multi-Center Cohort Study By Eric, the European Research Initiative on CLL, in Harmony

Author

Mansouri, Larry, primary, Thorvaldsdottir, Birna, additional, Sutton, Lesley-Ann, additional, Meggendorfer, Manja, additional, Nadeu, Ferran, additional, Brieghel, Christian, additional, Parker, Helen, additional, Laidou, Stamatia, additional, Moia, Riccardo, additional, Rossi, Davide, additional, Catherwood, Mark, additional, Kotaskova, Jana, additional, Delgado, Julio, additional, Rodríguez-Vicente, Ana E, additional, Benito, Rocio, additional, Rigolin, Gian Matteo, additional, Bonfiglio, Silvia, additional, Scarfo, Lydia, additional, Mattsson, Mattias, additional, Davis, Zadie, additional, Gogia, Ajay, additional, Rani, Lata, additional, Baliakas, Panagiotis, additional, Jylhä, Cecilia, additional, Skaftason, Aron, additional, Rapado, Inmaculada, additional, Miras, Fatima, additional, Martinez-Lopez, Joaquin, additional, de la Serna, Javier, additional, Hernández Rivas, Jesús M, additional, Thornton, Patrick, additional, Larrayoz, Maria Jose, additional, Calasanz, María José, additional, Mátrai, Zoltán, additional, Bodor, Csaba, additional, Smedby, Karin E., additional, Espinet, Blanca, additional, Puiggros, Anna, additional, Gupta, Ritu, additional, Bullinger, Lars, additional, Bosch, Francesc, additional, Tazón, Bárbara, additional, Baran-Marszak, Fanny, additional, Oscier, David, additional, Nguyen-Khac, Florence, additional, Zenz, Thorsten, additional, Terol, María José, additional, Cuneo, Antonio, additional, Hernández-Sánchez, María, additional, Pospisilova, Sarka, additional, Mills, Ken I, additional, Gaidano, Gianluca, additional, Niemann, Carsten Utoft, additional, Campo, Elías, additional, Strefford, Jonathan C, additional, Ghia, Paolo, additional, Stamatopoulos, Kostas, additional, and Rosenquist, Richard, additional

Published
2021
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20. A single-tube multiplex method for monitoring mutations in cysteine 481 of Bruton Tyrosine Kinase (BTK) gene in chronic lymphocytic leukemia patients treated with ibrutinib

Author

Maffei, Rossana, Fiorcari, Stefania, Atene, Claudio Giacinto, Martinelli, Silvia, Scarfo, Lydia, Bonfiglio, Silvia, Maccaferri, Monica, Ljungström, Viktor, Zucchini, Patrizia, Forghieri, Fabio, Potenza, Leonardo, Ghia, Paolo, Marasca, Roberto, Trenti, Tommaso, Tagliafico, Enrico, Luppi, Mario, Maffei, Rossana, Fiorcari, Stefania, Atene, Claudio Giacinto, Martinelli, Silvia, Scarfo, Lydia, Bonfiglio, Silvia, Maccaferri, Monica, Ljungström, Viktor, Zucchini, Patrizia, Forghieri, Fabio, Potenza, Leonardo, Ghia, Paolo, Marasca, Roberto, Trenti, Tommaso, Tagliafico, Enrico, and Luppi, Mario

Published
2021
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21. Laboratories Can Reliably Detect Clinically Relevant Variants in the TP53 Gene below 10 % Allelic Frequency: A Multicenter Study of ERIC, the European Research Initiative on CLL

Author

Pavlova, Sarka, Malcikova, Jitka, Radova, Lenka, Bonfiglio, Silvia, Cowland, Jack B., Brieghel, Christian, Andersen, Mette Klarskov, Karypidou, Maria, Biderman, Bella V, Doubek, Michael, Lazarian, Gregory, Rapado, Inmaculada, Vynck, Matthijs, Porret, Naomi, Andres, Martin, Rosenberg, Dina, Sahar, Dvora, Martinez-Laperche, Carolina, Borde, Ismael Buño, Hindley, Andrew, Sánchez, Julio Bravo, García-Marco, José, Serrano, Alicia, Ferrer Lores, Blanca, Fernández-Rodriguez, Concepción, Bellosillo, Beatriz, Stilgenbauer, Stephan, Tausch, Eugen, Nikdin, Hero, Quinn, Fiona, Atkinson, Emer, Van De Corput, Lisette, Yildiz, Cafer, Bilbao, Cristina, Florido, Yanira, Thiede, Christian, Schuster, Caroline, Stoj, Anastazja, Czekalska, Sylwia, Chatzidimitriou, Anastasia, Laidou, Stamatia, Bidet, Audrey, Dussiau, Charles, Nollet, Friedel, Piras, Giovanna, Borosova, Tereza, Kurucova, Terezia, Monne, Maria, Smirnova, Svetlana, Nikitin, Evgeny, Sloma, Ivan, Delfau, Marie-Helene, Largeaud, Laetitia, Ysebaert, Loic, Valk, Peter J. M., Christian, Amy, Walewska, Renata, Sebastião, Marta, da Silva, Maria Gomes, Galieni, Piero, Angelini, Mario, Rossi, Davide, Spina, Valeria, Matos, Sónia, Martins, Vânia, Donaldson, David, Stoklosa, Tomasz, Pepek, Monika, Baliakas, Panagiotis, Andreu, Rafa, Luna, Irene, Kahre, Tiina, Murumets, Ülle, Laird, Sophie, Ward, Daniel, Alcoceba, Miguel, Balanzategui, Ana, Scarfo, Lydia, Gandini, Francesca, Zapparoli, Ettore, Blanco, Adoracion, Costa, Pau Abrisqueta, Rodriguez, Ana E., Benito Sanchez, Maria Rocio, Davi, Frédéric, Bravetti, Clothilde, Gameiro, Paula, Martinez-Lopez, Joaquin, Tazon, Barbara, Baran-Marszak, Fanny, Davies, Zadie, Caterwood, Mark, Sudarikov, Andrey B, Rosenquist, Richard, Niemann, Carsten Utoft, Stamatopoulos, Kostas, Ghia, Paolo, and Pospisilova, Sarka

Published
2023
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22. A single-tube multiplex method for monitoring mutations in cysteine 481 of Bruton Tyrosine Kinase (BTK) gene in chronic lymphocytic leukemia patients treated with ibrutinib

Author

Maffei, Rossana, primary, Fiorcari, Stefania, additional, Atene, Claudio Giacinto, additional, Martinelli, Silvia, additional, Scarfò, Lydia, additional, Bonfiglio, Silvia, additional, Maccaferri, Monica, additional, Ljungström, Viktor, additional, Zucchini, Patrizia, additional, Forghieri, Fabio, additional, Potenza, Leonardo, additional, Ghia, Paolo, additional, Marasca, Roberto, additional, Trenti, Tommaso, additional, Tagliafico, Enrico, additional, and Luppi, Mario, additional

Published
2021
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23. Next Generation Sequencing in Non-Small Cell Lung Cancer: Pitfalls and Opportunities

Author

Lazzari, Chiara, primary, Bulotta, Alessandra, additional, Cangi, Maria Giulia, additional, Bucci, Gabriele, additional, Pecciarini, Lorenza, additional, Bonfiglio, Silvia, additional, Lorusso, Vincenza, additional, Ippati, Stefania, additional, Arrigoni, Gianluigi, additional, Grassini, Greta, additional, Doglioni, Claudio, additional, and Gregorc, Vanesa, additional

Published
2020
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24. Mutations of the Exportin 1 (XPO1) Gene Predict Shorter Time to First Treatment in 1092 Early Stage Chronic Lymphocytic Leukemia Patients. Α Training/Validation Study

Author

Moia, Riccardo, primary, Favini, Chiara, additional, Ferri, Valentina, additional, Bomben, Riccardo, additional, Sagiraju, Sruthi, additional, Bittolo, Tamara, additional, Scarfo, Lydia, additional, Bonfiglio, Silvia, additional, Maffei, Rossana, additional, Baldoni, Stefano, additional, Raponi, Sara, additional, Spina, Valeria, additional, Bruscaggin, Alessio, additional, Terzi di Bergamo, Lodovico, additional, De Paoli, Lorenzo, additional, Margiotta Casaluci, Gloria, additional, Deambrogi, Clara, additional, Rasi, Silvia, additional, Condoluci, Adalgisa, additional, Kodipad, Ahad Ahmed, additional, Adhinaveni, Ramesh, additional, Mokabari, Katia, additional, Mahmoud, Abdurraouf Mokhtar, additional, Patriarca, Andrea, additional, Olivieri, Jacopo, additional, D'Arena, Giovanni, additional, Zaja, Francesco, additional, Chiarenza, Annalisa, additional, Del Poeta, Giovanni, additional, Zucchetto, Antonella, additional, Rossi, Francesca Maria, additional, Del Giudice, Ilaria, additional, Sportoletti, Paolo, additional, Marasca, Roberto, additional, Ghia, Paolo, additional, Foà, Robin, additional, Gaidano, Gianluca, additional, Rossi, Davide, additional, and Gattei, Valter, additional

Published
2020
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25. A CD8α- Subset of CD4+SLAMF7+ Cytotoxic T Cells Is Expanded in Patients With IgG4-Related Disease and Decreases Following Glucocorticoid Treatment

Author

Della-Torre, Emanuel, Bozzalla-Cassione, Emanuele, Sciorati, Clara, Ruggiero, Eliana, Lanzillotta, Marco, Bonfiglio, Silvia, Mattoo, Hamid, Perugino, Cory A, Bozzolo, Enrica, Rovati, Lucrezia, Arcidiacono, Paolo Giorgio, Balzano, Gianpaolo, Lazarevic, Dejan, Bonini, Chiara, Falconi, Massimo, Stone, John H, Dagna, Lorenzo, Pillai, Shiv, Manfredi, Angelo A, DELLA TORRE , EMANUEL, Della-Torre, Emanuel, Bozzalla-Cassione, Emanuele, Sciorati, Clara, Ruggiero, Eliana, Lanzillotta, Marco, Bonfiglio, Silvia, Mattoo, Hamid, Perugino, Cory A, Bozzolo, Enrica, Rovati, Lucrezia, Arcidiacono, Paolo Giorgio, Balzano, Gianpaolo, Lazarevic, Dejan, Bonini, Chiara, Falconi, Massimo, Stone, John H, Dagna, Lorenzo, Pillai, Shiv, Manfredi, Angelo A, and DELLA TORRE, Emanuel

Subjects
0301 basic medicine, CD4-Positive T-Lymphocytes, Male, cytomegaloviru, T cell, CD8 Antigens, Receptors, Antigen, T-Cell, alpha-beta, Immunology, Population, Granzymes, Article, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Antigen, Signaling Lymphocytic Activation Molecule Family, parasitic diseases, medicine, Immunology and Allergy, Cytotoxic T cell, Humans, education, IgG4-related disease, Glucocorticoids, Aged, 030203 arthritis & rheumatology, IgG4, education.field_of_study, biology, medicine.diagnostic_test, glucocorticoids, Chemistry, Perforin, T-cell receptor, Middle Aged, Flow Cytometry, CD4 cytotoxic T cell, 030104 developmental biology, medicine.anatomical_structure, Treatment Outcome, Cancer research, Granzyme A, biology.protein, Female, Immunoglobulin G4-Related Disease, T-Lymphocytes, Cytotoxic
Abstract

Objective An unconventional population of CD4+ signaling lymphocytic activation molecule family member 7-positive (SLAMF7+) cytotoxic effector memory T (TEM ) cells (CD4+ cytotoxic T lymphocytes [CTLs]) has been linked causally to IgG4-related disease (IgG4-RD). Glucocorticoids represent the first-line therapeutic approach in patients with IgG4-RD, but their mechanism of action in this specific condition remains unknown. We undertook this study to determine the impact of glucocorticoids on CD4+ CTLs in IgG4-RD. Methods Expression of CD8α, granzyme A, perforin, and SLAMF7 within the effector memory compartment of CD45RO+ (TEM ) and CD45RA+ effector memory T (TEMRA ) CD4+ cells was quantified by flow cytometry in 18 patients with active IgG4-RD, both at baseline and after 6 months of glucocorticoid treatment. Eighteen healthy subjects were studied as controls. Next-generation sequencing of the T cell receptor α- and β-chain gene was performed on circulating CD4+ CTLs from patients with IgG4-RD before and after treatment and in affected tissues. Results Circulating CD4+ TEM and TEMRA cells were not expanded in IgG4-RD patients compared to healthy controls. CD4+SLAMF7+ TEM cells (but not TEMRA cells) were significantly increased among IgG4-RD patients. Within CD4+SLAMF7+ TEM cells, CD8α- cells but not CD8αlow cells were elevated in IgG4-RD patients. The same dominant clones of CD8α-CD4+SLAMF7+ TEM cells found in peripheral blood were also identified in affected tissue. CD8α- and CD8αlow CD4+SLAMF7+ TEM cells both expressed cytolytic molecules. Clonally expanded CD8α- but not CD8αlow CD4+SLAMF7+ TEM cells decreased following glucocorticoid-induced disease remission. Conclusion A subset of CD8α-CD4+SLAMF7+ cytotoxic TEM cells is oligoclonally expanded in patients with active IgG4-RD. This TEM cell population contracts following glucocorticoid-induced remission. Further characterization of this cell population may provide prognostic information and targets for therapeutic intervention.

Published
2017

26. BTK Leu528Trp - a Potential Secondary Resistance Mechanism Specific for Patients with Chronic Lymphocytic Leukemia Treated with the Next Generation BTK Inhibitor Zanubrutinib

Author

Handunnetti, Sasanka M., primary, Tang, Chloe Pek Sang, primary, Nguyen, Tamia, primary, Zhou, Xing, primary, Thompson, Ella, primary, Sun, Hanzi, primary, Xing, Haimei, primary, Zhang, Bo, primary, Guo, Yin, primary, Sutton, Lesley Ann, primary, Ghia, Paolo, primary, Rosenquist, Richard, primary, Scarfo, Lydia, primary, Bonfiglio, Silvia, primary, Seymour, John F., primary, Anderson, Mary Ann, primary, Roberts, Andrew W., primary, Huang, David C.S., primary, Liu, Ye, primary, Cheah, Chan Y., primary, Westerman, David Alan, primary, Yeh, Paul Sung-Hao, primary, Tam, Constantine S., primary, and Blombery, Piers, primary

Published
2019
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27. High Surface IgM Levels Associate with Shorter Response Duration and Bypass of the BTK Blockade during Ibrutinib Therapy in CLL Patients

Author

Chiodin, Giorgia, primary, Dutton, David, additional, Martino, Enrica Antonia, additional, Drennan, Samantha, additional, Tracy, Ian, additional, Ondrisova, Laura, additional, Henderson, Isla, additional, D'Avola, Annalisa, additional, Pitsillidou, Christina, additional, Mraz, Marek, additional, Johnson, Peter, additional, Duncombe, Andrew, additional, Packham, Graham, additional, Steele, Andrew J, additional, Parker, Helen, additional, Bonfiglio, Silvia, additional, Scarfo, Lydia, additional, Sutton, Lesley-Ann, additional, Ghia, Paolo, additional, Rose-Zerilli, Matthew John Jerome, additional, Strefford, Jonathan C, additional, Stevenson, Freda K., additional, and Forconi, Francesco, additional

Published
2019
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28. Integrated Somatic and Germline Whole-Exome Sequencing Analysis in Women with Lung Cancer after a Previous Breast Cancer

Author

Coco, Simona, primary, Bonfiglio, Silvia, additional, Cittaro, Davide, additional, Vanni, Irene, additional, Mora, Marco, additional, Genova, Carlo, additional, Dal Bello, Maria, additional, Boccardo, Simona, additional, Alama, Angela, additional, Rijavec, Erika, additional, Sini, Claudio, additional, Rossella, Valeria, additional, Barletta, Giulia, additional, Biello, Federica, additional, Truini, Anna, additional, Bruzzo, Cristina, additional, Gallo, Maurizio, additional, Lazarevic, Dejan, additional, Ballestrero, Alberto, additional, and Grossi, Francesco, additional

Published
2019
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29. A CD8α− Subset of CD4+SLAMF7+ Cytotoxic T Cells Is Expanded in Patients With IgG4-Related Disease and Decreases Following Glucocorticoid Treatment

Author

Della-Torre, Emanuel, primary, Bozzalla-Cassione, Emanuele, additional, Sciorati, Clara, additional, Ruggiero, Eliana, additional, Lanzillotta, Marco, additional, Bonfiglio, Silvia, additional, Mattoo, Hamid, additional, Perugino, Cory A., additional, Bozzolo, Enrica, additional, Rovati, Lucrezia, additional, Arcidiacono, Paolo Giorgio, additional, Balzano, Gianpaolo, additional, Lazarevic, Dejan, additional, Bonini, Chiara, additional, Falconi, Massimo, additional, Stone, John H., additional, Dagna, Lorenzo, additional, Pillai, Shiv, additional, and Manfredi, Angelo A., additional

Published
2018
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30. A Whole-Exome Sequencing Study In Multiple Sclerosis Multiplex Families (P2.389)

Author

Mascia, Elisabetta, primary, Zauli, Andrea, additional, Guaschino, Clara, additional, Sorosina, Melissa, additional, Santoro, Silvia, additional, Biancolini, Donatella, additional, Bonfiglio, Silvia, additional, Lazarevic, Dejan, additional, Meola, Giovanni, additional, Martinelli, Vittorio, additional, Tonon, Giovanni, additional, Comi, Giancarlo, additional, Esposito, Federica, additional, and Boneschi, Filippo Martinelli, additional

Published
2018
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31. Additional file 1: Figure S1Â and Figure S2. of Performance comparison of two commercial human whole-exome capture systems on formalin-fixed paraffin-embedded lung adenocarcinoma samples

Author

Bonfiglio, Silvia, Vanni, Irene, Rossella, Valeria, Truini, Anna, Lazarevic, Dejan, Bello, Maria Giovanna Dal, Alama, Angela, Mora, Marco, Rijavec, Erika, Genova, Carlo, Cittaro, Davide, Grossi, Francesco, and Coco, Simona

Abstract

Figure S1. DNA quality control. TapeStation profiles of gDNA isolated from FF and matching FFPE block tumor tissues from 5 lung ADC patients. In each profile, the DIN, indicative of gDNA degradation status, is also displayed (numerical assessment ranges from 10 for undamaged gDNA, to 1 for highly fragmented gDNA) (a). The Table reports the gDNA concentration (ng/ul) assessed by NanoDrop, Qubit, and TapeStation, and purity (260/280 and 260/230) (b). Additionally, AYR and DIN parameters, indicative of FFPE gDNA fragmentation status, evaluated by a multiple PCR assay and TapeStation respectively, are reported. Image of agarose gel 1Â % shows the gDNA smears indicative of the different degradation status of FF and FFPE gDNAs (c). Figure S2. The workflow illustrates samples processing and WES data analysis for both exome enrichment platforms. (PDF 187 kb)

Published
2016
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32. Multi-omics profiling in multiplex Italian families with Multiple Sclerosis: the ITALIANO study (P3.377)

Author

Mascia, Elisabetta, primary, Guaschino, Clara, additional, Zauli, Andrea, additional, Sorosina, Melissa, additional, Esposito, Federica, additional, Osiceanu, Ana, additional, Bonfiglio, Silvia, additional, Lazarevic, Dejan, additional, Protti, Alessandra, additional, Moiola, Lucia, additional, Martinelli, Vittorio, additional, Meola, Giovanni, additional, Comi, Giancarlo, additional, D’Alfonso, Sandra, additional, and Boneschi, Filippo Martinelli, additional

Published
2017
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33. Whole exome sequencing of independent lung adenocarcinoma, lung squamous cell carcinoma, and malignant peritoneal mesothelioma

Author

Vanni, Irene, primary, Coco, Simona, additional, Bonfiglio, Silvia, additional, Cittaro, Davide, additional, Genova, Carlo, additional, Biello, Federica, additional, Mora, Marco, additional, Rossella, Valeria, additional, Dal Bello, Maria Giovanna, additional, Truini, Anna, additional, Banelli, Barbara, additional, Lazarevic, Dejan, additional, Alama, Angela, additional, Rijavec, Erika, additional, Barletta, Giulia, additional, and Grossi, Francesco, additional

Published
2016
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34. Immunoglobulin gene analysis in chronic lymphocytic leukemia in the era of next generation sequencing

Author

Davi, Frédéric, Langerak, Anton W., de Septenville, Anne Langlois, Kolijn, P. Martijn, Hengeveld, Paul J., Chatzidimitriou, Anastasia, Bonfiglio, Silvia, Sutton, Lesley-Ann, Rosenquist, Richard, Ghia, Paolo, and Stamatopoulos, Kostas

Abstract

Twenty years after landmark publications, there is a consensus that the somatic hypermutation (SHM) status of the clonotypic immunoglobulin heavy variable (IGHV) gene is an important cornerstone for accurate risk stratification and therapeutic decision-making in patients with chronic lymphocytic leukemia (CLL). The IGHV SHM status has traditionally been determined by conventional Sanger sequencing. However, NGS has heralded a new era in medical diagnostics and immunogenetic analysis is following this trend. There is indeed a growing demand for shifting practice and using NGS for IGHV gene SHM assessment, although it is debatable whether it is always justifiable, at least taking into account financial considerations for laboratories with limited resources. Nevertheless, as this analysis impacts on treatment decisions, standardization of both technical aspects, and data interpretation becomes essential. Also, the need for establishing new recommendations and providing dedicated education and training on NGS-based immunogenetics is greater than ever before. Here we address potential and challenges of NGS-based immunogenetics in CLL. We are convinced that this perspective helps the hematological community to better understand the pros and cons of this new technological development for CLL patient management.

Published
2020
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35. Performance comparison of two commercial human whole-exome capture systems on formalin-fixed paraffin-embedded lung adenocarcinoma samples

Author

Bonfiglio, Silvia, primary, Vanni, Irene, additional, Rossella, Valeria, additional, Truini, Anna, additional, Lazarevic, Dejan, additional, Dal Bello, Maria Giovanna, additional, Alama, Angela, additional, Mora, Marco, additional, Rijavec, Erika, additional, Genova, Carlo, additional, Cittaro, Davide, additional, Grossi, Francesco, additional, and Coco, Simona, additional

Published
2016
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36. Exome sequencing and pathway analysis for identification of genetic variability relevant for bronchopulmonary dysplasia (BPD) in preterm newborns: A pilot study

Author

Carrera, Paola, Diresta, Chiara, Volonteri, Chiara, Castiglioni, Emanuela, Bonfiglio, Silvia, Lazarevic, Dejan, Cittaro, Davide, Stupkad, Elia, Ferrari, Maurizio, Somaschini, Marco, Magaldi, Rosario, Rinaldi, Matteo, Maffei, Gianfranco, Stronati, Mauro, Tzialla, Chryssoula, Borghesi, Alessandro, Tagliabue, Paolo, Fedeli, Tiziana, Citterio, Marco, Mosca, Fabio, Colnaghi, Mariarosa, Lavizzari, Anna, Agosti, Massimo, Francescato, Gaia, Pomero, Giulia, Dalmazzo, Cristina, Boldrini, Antonio, Scaramuzzo, Rosa, Bertino, Enrico, Borgione, Silvia, Martano, Claudio, Carnielli, Virgilio, Nobile, Stefano, Auriemma, Antonietta, Bellan, Cristina, Carrera, Giuseppe, Zambetti, Chiara, Pucello, Riccardo, Palatta, Sara, Stefano Nobile (ORCID:0000-0002-5304-1485), Carrera, Paola, Diresta, Chiara, Volonteri, Chiara, Castiglioni, Emanuela, Bonfiglio, Silvia, Lazarevic, Dejan, Cittaro, Davide, Stupkad, Elia, Ferrari, Maurizio, Somaschini, Marco, Magaldi, Rosario, Rinaldi, Matteo, Maffei, Gianfranco, Stronati, Mauro, Tzialla, Chryssoula, Borghesi, Alessandro, Tagliabue, Paolo, Fedeli, Tiziana, Citterio, Marco, Mosca, Fabio, Colnaghi, Mariarosa, Lavizzari, Anna, Agosti, Massimo, Francescato, Gaia, Pomero, Giulia, Dalmazzo, Cristina, Boldrini, Antonio, Scaramuzzo, Rosa, Bertino, Enrico, Borgione, Silvia, Martano, Claudio, Carnielli, Virgilio, Nobile, Stefano, Auriemma, Antonietta, Bellan, Cristina, Carrera, Giuseppe, Zambetti, Chiara, Pucello, Riccardo, Palatta, Sara, and Stefano Nobile (ORCID:0000-0002-5304-1485)

Abstract

Background: Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in infancy, affecting preterm children with low birth weight. The disease has a multifactorial aetiology with a significant genetic component; until now published association studies have identified several candidate genes but only few of these data has been replicated. In this pilot study, we approached exome sequencing aimed at identifying non-common variants, which are expected to have a stronger phenotypic effect. Materials and methods: We performed this study on 26 Italian severely affected BPD preterm unrelated newborns, homogeneously selected from a large prospective cohort. We used an Illumina HiSeq 2000 for sequencing. Data analysis was focussed on genes previously associated to BPD susceptibility and to new candidates in related pathways, highlighted by a prioritization analysis performed using ToppGene Suite. Results: By exome sequencing, we identified 3369 novel variants, with a median of 400 variations per sample. The top candidate genes highlighted were NOS2, MMP1, CRP, LBP and the toll-like receptor (. TLR) family. All of them have been confirmed with Sanger sequencing. Conclusions: Potential candidate genes have been discovered in this preliminary study; the pathogenic role of identified variants will need to be confirmed with functional and segregation studies and possibly with further methods, able to evaluate the collective influence of rare variants.Moreover, additional candidates will be tested and genetic analysis will be extended to all affected children.

Published
2015

37. Exome sequencing and pathway analysis for identification of genetic variability relevant for bronchopulmonary dysplasia (BPD) in preterm newborns: A pilot study

Author

Carrera, Paola, primary, Di Resta, Chiara, additional, Volonteri, Chiara, additional, Castiglioni, Emanuela, additional, Bonfiglio, Silvia, additional, Lazarevic, Dejan, additional, Cittaro, Davide, additional, Stupka, Elia, additional, Ferrari, Maurizio, additional, Somaschini, Marco, additional, Magaldi, Rosario, additional, Rinaldi, Matteo, additional, Maffei, Gianfranco, additional, Stronati, Mauro, additional, Tzialla, Chryssoula, additional, Borghesi, Alessandro, additional, Tagliabue, Paolo, additional, Fedeli, Tiziana, additional, Citterio, Marco, additional, Mosca, Fabio, additional, Colnaghi, Mariarosa, additional, Lavizzari, Anna, additional, Agosti, Massimo, additional, Francescato, Gaia, additional, Pomero, Giulia, additional, Dalmazzo, Cristina, additional, Boldrini, Antonio, additional, Scaramuzzo, Rosa, additional, Bertino, Enrico, additional, Borgione, Silvia, additional, Martano, Claudio, additional, Carnielli, Virgilio, additional, Nobile, Stefano, additional, Auriemma, Antonietta, additional, Bellan, Cristina, additional, Carrera, Giuseppe, additional, Zambetti, Chiara, additional, Pucello, Riccardo, additional, and Palatta, Sara, additional

Published
2015
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38. Laboratories Can Reliably Detect Clinically Relevant Variants in the TP53Gene below 10 % Allelic Frequency: A Multicenter Study of ERIC, the European Research Initiative on CLL

Author

Pavlova, Sarka, Malcikova, Jitka, Radova, Lenka, Bonfiglio, Silvia, Cowland, Jack B., Brieghel, Christian, Andersen, Mette Klarskov, Karypidou, Maria, Biderman, Bella V, Doubek, Michael, Lazarian, Gregory, Rapado, Inmaculada, Vynck, Matthijs, Porret, Naomi, Andres, Martin, Rosenberg, Dina, Sahar, Dvora, Martinez-Laperche, Carolina, Borde, Ismael Buño, Hindley, Andrew, Sánchez, Julio Bravo, García-Marco, José, Serrano, Alicia, Ferrer Lores, Blanca, Fernández-Rodriguez, Concepción, Bellosillo, Beatriz, Stilgenbauer, Stephan, Tausch, Eugen, Nikdin, Hero, Quinn, Fiona, Atkinson, Emer, Van De Corput, Lisette, Yildiz, Cafer, Bilbao, Cristina, Florido, Yanira, Thiede, Christian, Schuster, Caroline, Stoj, Anastazja, Czekalska, Sylwia, Chatzidimitriou, Anastasia, Laidou, Stamatia, Bidet, Audrey, Dussiau, Charles, Nollet, Friedel, Piras, Giovanna, Borosova, Tereza, Kurucova, Terezia, Monne, Maria, Smirnova, Svetlana, Nikitin, Evgeny, Sloma, Ivan, Delfau, Marie-Helene, Largeaud, Laetitia, Ysebaert, Loic, Valk, Peter J. M., Christian, Amy, Walewska, Renata, Sebastião, Marta, da Silva, Maria Gomes, Galieni, Piero, Angelini, Mario, Rossi, Davide, Spina, Valeria, Matos, Sónia, Martins, Vânia, Donaldson, David, Stoklosa, Tomasz, Pepek, Monika, Baliakas, Panagiotis, Andreu, Rafa, Luna, Irene, Kahre, Tiina, Murumets, Ülle, Laird, Sophie, Ward, Daniel, Alcoceba, Miguel, Balanzategui, Ana, Scarfo, Lydia, Gandini, Francesca, Zapparoli, Ettore, Blanco, Adoracion, Costa, Pau Abrisqueta, Rodriguez, Ana E., Benito Sanchez, Maria Rocio, Davi, Frédéric, Bravetti, Clothilde, Gameiro, Paula, Martinez-Lopez, Joaquin, Tazon, Barbara, Baran-Marszak, Fanny, Davies, Zadie, Caterwood, Mark, Sudarikov, Andrey B, Rosenquist, Richard, Niemann, Carsten Utoft, Stamatopoulos, Kostas, Ghia, Paolo, and Pospisilova, Sarka

Abstract

The presence of mutations in the TP53gene is a powerful prognostic and predictive marker in chronic lymphocytic leukemia (CLL). Widespread use of NGS has enabled the detection of variants ≤10 % variant allelic frequency (low-VAF variants); however, the overall reliability and reproducibility of NGS techniques to identify such variants have been questioned repeatedly. Individual studies using sensitive, custom NGS-based assays have mostly demonstrated the shortened overall survival (OS) and event-free survival in patients with low-VAF TP53variants treated with chemoimmunotherapy (CIT) regimens with median survival ranging between that of TP53 variants >10 % VAF (high-VAF) and wild-type TP53(wt- TP53).

Published
2023
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40. Mitogenomes from Egyptian Cattle Breeds: New Clues on the Origin of Haplogroup Q and the Early Spread of Bos taurus from the Near East

Author

Olivieri, Anna, primary, Gandini, Francesca, additional, Achilli, Alessandro, additional, Fichera, Alessandro, additional, Rizzi, Ermanno, additional, Bonfiglio, Silvia, additional, Battaglia, Vincenza, additional, Brandini, Stefania, additional, De Gaetano, Anna, additional, El-Beltagi, Ahmed, additional, Lancioni, Hovirag, additional, Agha, Saif, additional, Semino, Ornella, additional, Ferretti, Luca, additional, and Torroni, Antonio, additional

Published
2015
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42. The Enigmatic Origin of Bovine mtDNA Haplogroup R: Sporadic Interbreeding or an Independent Event of Bos primigenius Domestication in Italy?

Author

Bonfiglio, Silvia, Achilli, Alessandro, Olivieri, Anna, Negrini, Riccardo, Colli, Licia, Liotta, Luigi, Ajmone Marsan, Paolo, Torroni, Antonio, Ferretti, Luca, Negrini, Riccardo (ORCID:0000-0002-8735-0286), Colli, Licia (ORCID:0000-0002-7221-2905), Ajmone Marsan, Paolo (ORCID:0000-0003-3165-4579), Bonfiglio, Silvia, Achilli, Alessandro, Olivieri, Anna, Negrini, Riccardo, Colli, Licia, Liotta, Luigi, Ajmone Marsan, Paolo, Torroni, Antonio, Ferretti, Luca, Negrini, Riccardo (ORCID:0000-0002-8735-0286), Colli, Licia (ORCID:0000-0002-7221-2905), and Ajmone Marsan, Paolo (ORCID:0000-0003-3165-4579)

Published
2010

43. Characterisation and Validation of Insertions and Deletions in 173 Patient Exomes

Author

Lescai, Francesco, primary, Bonfiglio, Silvia, additional, Bacchelli, Chiara, additional, Chanudet, Estelle, additional, Waters, Aoife, additional, Sisodiya, Sanjay M., additional, Kasperavičiūtė, Dalia, additional, Williams, Julie, additional, Harold, Denise, additional, Hardy, John, additional, Kleta, Robert, additional, Cirak, Sebahattin, additional, Williams, Richard, additional, Achermann, John C., additional, Anderson, John, additional, Kelsell, David, additional, Vulliamy, Tom, additional, Houlden, Henry, additional, Wood, Nicholas, additional, Sheerin, Una, additional, Tonini, Gian Paolo, additional, Mackay, Donna, additional, Hussain, Khalid, additional, Sowden, Jane, additional, Kinsler, Veronica, additional, Osinska, Justyna, additional, Brooks, Tony, additional, Hubank, Mike, additional, Beales, Philip, additional, and Stupka, Elia, additional

Published
2012
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44. Origin and Spread of Bos taurus: New Clues from Mitochondrial Genomes Belonging to Haplogroup T1

Author

Bonfiglio, Silvia, primary, Ginja, Catarina, additional, De Gaetano, Anna, additional, Achilli, Alessandro, additional, Olivieri, Anna, additional, Colli, Licia, additional, Tesfaye, Kassahun, additional, Agha, Saif Hassan, additional, Gama, Luis T., additional, Cattonaro, Federica, additional, Penedo, M. Cecilia T, additional, Ajmone-Marsan, Paolo, additional, Torroni, Antonio, additional, and Ferretti, Luca, additional

Published
2012
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46. The Multifaceted Origin of Taurine Cattle Reflected by the Mitochondrial Genome

Author

Achilli, Alessandro, primary, Bonfiglio, Silvia, additional, Olivieri, Anna, additional, Malusà, Arianna, additional, Pala, Maria, additional, Kashani, Baharak Hooshiar, additional, Perego, Ugo A., additional, Ajmone-Marsan, Paolo, additional, Liotta, Luigi, additional, Semino, Ornella, additional, Bandelt, Hans-Jürgen, additional, Ferretti, Luca, additional, and Torroni, Antonio, additional

Published
2009
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47. BTKand PLCG2remain unmutated in one third of patients with CLL relapsing on ibrutinib

Author

Bonfiglio, Silvia, Sutton, Lesley-Ann, Ljungström, Viktor, Capasso, Antonella, Pandzic, Tatjana, Weström, Simone, Foroughi-Asl, Hassan, Skaftason, Aron, Gellerbring, Anna, Lyander, Anna, Gandini, Francesca, Gaidano, Gianluca, Trentin, Livio, Bonello, Lisa, Reda, Gianluigi, Bödör, Csaba, Stavroyianni, Niki, Tam, Constantine S., Marasca, Roberto, Forconi, Francesco, Panayiotidis, Panayiotis, Ringshausen, Ingo, Jaksic, Ozren, Frustaci, Anna Maria, Iyengar, Sunil, Coscia, Marta, Mulligan, Stephen P., Ysebaert, Loïc, Strugov, Vladimir, Pavlovsky, Carolina, Walewska, Renata, Österborg, Anders, Cortese, Diego, Ranghetti, Pamela, Baliakas, Panagiotis, Stamatopoulos, Kostas, Scarfò, Lydia, Rosenquist, Richard, and Ghia, Paolo

Abstract

•One third of patients with CLL relapsing on ibrutinib do not carry BTK/PLCG2mutations, even with a 0.1% sensitivity.•Additional mechanisms, such as del(8p), EGR2and NF-κB pathway mutations, may be cooperating in determining progression on ibrutinib.

Published
2023
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48. High surface IgM levels associate with shorter response to ibrutinib and BTK bypass in CLL patients

Author

Chiodin, Giorgia, Drennan, Samantha, Martino, Enrica Antonia, Ondrisova, Laura, Henderson, Isla, del Rio, Luis, Tracy, Ian, D’Avola, Annalisa, Parker, Helen, Bonfiglio, Silvia, Scarfo’, Lydia, Sutton, Lesley-Ann, Strefford, Jonathan C., Forster, Jade, Brake, Oliver, Potter, Kathleen N., Sale, Ben, Lanham, Stuart, Mraz, Marek, Ghia, Paolo, Stevenson, Freda K., and Forconi, Francesco

Abstract

Chronic lymphocytic leukemia (CLL) cells have variably low surface IgM (sIgM) levels/signaling capacity, influenced by chronic antigen engagement at tissue sites. Within these low levels, CLL with relatively high sIgM (CLLhigh) progress more rapidly than CLL with low sIgM (CLLlow). During ibrutinib therapy, surviving CLL cells redistribute into the peripheral blood and can recover sIgM expression. Return of CLL cells to tissue may eventually recur, where cells with high sIgM could promote tumor growth. We analyzed time to new treatment (TTNT) following ibrutinib in 70 CLL patients (median follow-up of 66 months) and correlated it with pre-treatment sIgM levels and signaling characteristics. Pre-treatment sIgM levels correlated with signaling capacity, as measured by intracellular Ca2+mobilization (iCa2+), in vitro(r=0.70; p<0.0001). High sIgM levels/signaling strongly correlated with short TTNT (p<0.05), and 36% CLLhighversus 8% CLLlowprogressed to require a new treatment. In vitro,capacity of ibrutinib to inhibit sIgM-mediated signaling inversely correlated with pre-therapy sIgM levels (r=-0.68, p=0.01) or iCa2+(r=-0.71, p=0.009). In patients, sIgM-mediated iCa2+and ERK phosphorylation levels were reduced by ibrutinib therapy, but not abolished. The residual signaling capacity downstream of BTK was associated with high expression of sIgM, while it was minimal when sIgM expression was low (p<0.05). These results suggested that high sIgM levels facilitated CLL cell resistance to ibrutinib in patients. The CLL cells, surviving in the periphery with high sIgM expression, include a dangerous fraction, able to migrate to tissue and receive proliferative stimuli, which may require targeting by combined approaches.

Published
2022
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49. Mutations of the Exportin 1 (XPO1)Gene Predict Shorter Time to First Treatment in 1092 Early Stage Chronic Lymphocytic Leukemia Patients. Α Training/Validation Study

Author

Moia, Riccardo, Favini, Chiara, Ferri, Valentina, Bomben, Riccardo, Sagiraju, Sruthi, Bittolo, Tamara, Scarfo, Lydia, Bonfiglio, Silvia, Maffei, Rossana, Baldoni, Stefano, Raponi, Sara, Spina, Valeria, Bruscaggin, Alessio, Terzi di Bergamo, Lodovico, De Paoli, Lorenzo, Margiotta Casaluci, Gloria, Deambrogi, Clara, Rasi, Silvia, Condoluci, Adalgisa, Kodipad, Ahad Ahmed, Adhinaveni, Ramesh, Mokabari, Katia, Mahmoud, Abdurraouf Mokhtar, Patriarca, Andrea, Olivieri, Jacopo, D'Arena, Giovanni, Zaja, Francesco, Chiarenza, Annalisa, Del Poeta, Giovanni, Zucchetto, Antonella, Rossi, Francesca Maria, Del Giudice, Ilaria, Sportoletti, Paolo, Marasca, Roberto, Ghia, Paolo, Foà, Robin, Gaidano, Gianluca, Rossi, Davide, and Gattei, Valter

Abstract

Background. Approximately 70% of newly diagnosed chronic lymphocytic leukemia (CLL) patients present in early Binet or Rai stage, may never require treatment, and may have a life expectancy similar to that of the general population. Two independent and recent studies have identified the clinical and immunogenetic variables associated with shorter time to first treatment (TTFT) in Binet A and Rai 0 CLL (Condoluci et al., Blood2020; Cohen et al., Haematologica2020). However, the clinical impact of gene mutations in predicting TTFT is not completely understood.

Published
2020
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50. Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY

Author

Mansouri, Larry, Thorvaldsdottir, Birna, Sutton, Lesley-Ann, Karakatsoulis, Georgios, Meggendorfer, Manja, Parker, Helen, Nadeu, Ferran, Brieghel, Christian, Laidou, Stamatia, Moia, Riccardo, Rossi, Davide, Catherwood, Mark, Kotaskova, Jana, Delgado, Julio, Rodríguez-Vicente, Ana E., Benito, Rocío, Rigolin, Gian Matteo, Bonfiglio, Silvia, Scarfo, Lydia, Mattsson, Mattias, Davis, Zadie, Gogia, Ajay, Rani, Lata, Baliakas, Panagiotis, Foroughi-Asl, Hassan, Jylhä, Cecilia, Skaftason, Aron, Rapado, Inmaculada, Miras, Fatima, Martinez-Lopez, Joaquín, de la Serna, Javier, Rivas, Jesús María Hernández, Thornton, Patrick, Larráyoz, María José, Calasanz, M.J, Fésüs, Viktória, Mátrai, Zoltán, Bödör, Csaba, Smedby, Karin E., Espinet, Blanca, Puiggros, Anna, Gupta, Ritu, Bullinger, Lars, Bosch José, Francesc Xavier, Tazón-Vega, Bárbara, Baran-Marszak, Fanny, Oscier, David, Nguyen-Khac, Florence, Zenz, Thorsten, Terol, Maria Jose, Cuneo, Antonio, Hernández-Sánchez, María, Pospisilova, Sarka, Mills, Ken, Gaidano, Gianluca, Niemann, Carsten U., Campo, Elias, Strefford, Jonathan C., Ghia, Paolo, Stamatopoulos, Kostas, Rosenquist, Richard, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Mansouri L, Thorvaldsdottir B, Sutton LA] Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. [Karakatsoulis G] Centre for Research and Technology Hellas, Institute of Applied Biosciences, Thessaloniki, Greece. Department of Mathematics, University of Ioannina, Ioannina, Greece. [Meggendorfer M] MLL Munich Leukemia Laboratory, Munich, Germany. [Parker H] Cancer Genomics, School for Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK. [Bosch F, Tazón-Vega B] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Karolinska Institutet [Stockholm], Institute of Applied Biosciences [Thessaloniki, Greece] (IAB), University of Ioannina, Munich Leukemia Laboratory [Munich, Germany] (M2L), University of Southampton, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Copenhagen University Hospital, Università degli Studi del Piemonte Orientale - Amedeo Avogadro (UPO), Oncology Institute of Southern Switzerland (IOSI), Institute Of Oncology Research [Bellinzona, Switzerland] (IOL), Queen's University [Belfast] (QUB), University Hospital Brno, Masaryk University [Brno] (MUNI), Clinic Barcelona Hospital Universitari, Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Università degli Studi di Ferrara = University of Ferrara (UniFE), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Uppsala University, University Hospitals Dorset NHS Foundation Trust [Bournemouth, UK] (UHD), All India Institute of Medical Sciences [New Delhi], Hospital Universitario 12 de Octubre [Madrid], Spanish National Cancer Research Center (CNIO), Hôpital de Beaumont [Dublin, Ireland] (HB), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), Navarra Institute for Health Research / Instituto de Investigación Sanitaria de Navarra (IdiSNA), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA)-Universidad de Navarra [Pamplona] (UNAV)-Clínica Universidad de Navarra [Pamplona], Semmelweis University [Budapest], South-Pest Hospital Centre [Budapest, Hungary] (SPHC), IMIM-Hospital del Mar, Generalitat de Catalunya, Humboldt University Of Berlin, Universitat Autònoma de Barcelona (UAB), Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Hôpital Avicenne HUPSSD - Service d'Hématologie Biologique, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universität Zürich [Zürich] = University of Zurich (UZH), University hospital of Zurich [Zurich], Universitat de València (UV), Centre for Research and Technology Hellas (CERTH), Karolinska University Hospital [Stockholm], and Baran-Marszak, Fanny

Subjects
Cancer Research, Otros calificadores::Otros calificadores::/genética [Otros calificadores], [SDV]Life Sciences [q-bio], Leucèmia limfocítica crònica - Aspectes genètics, Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES], Hematology, [SDV] Life Sciences [q-bio], Anomalies cromosòmiques, Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Lymphoid::Leukemia, B-Cell::Leukemia, Lymphocytic, Chronic, B-Cell [DISEASES], Oncology, Genetics research, Other subheadings::Other subheadings::/genetics [Other subheadings], Cancer genetics, fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS], neoplasias::neoplasias por tipo histológico::leucemia::leucemia linfoide::leucemia de células B::leucemia linfocítica crónica de células B [ENFERMEDADES]
Abstract

Cancer genetics; Genetics research Genètica del càncer; Recerca genètica Genética del cáncer; Investigación genética Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3–9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management. The European Research Initiative on CLL (ERIC) is a partner in the HARMONY Alliance, the EHA Scientific Working group on CLL and the ELN Workpackage 7 on CLL. This work was in part supported by; Associazione Italiana per la Ricerca sul Cancro—AIRC, Milano, Italy (Investigator Grant #20246 and Special Program on Metastatic Disease—5 per mille #21198); ERA NET TRANSCAN-2 Joint Transnational Call for Proposals: JTC 2014 (project #143 GCH-CLL) and JTC 2016 (project #179 NOVEL), project code (MIS) 5041673; Bando della Ricerca Finalizzata 2018, Ministero della Salute, Roma, Italy (progetto RF-2018–12368231); “la Caixa” Foundation (Health Research 2017 Program HR17-00221); the American Association for Cancer Research (2021 AACR-Amgen Fellowship in Clinical/Translational Cancer Research, 21-40-11-NADE), the European Hematology Association (EHA Junior Research Grant 2021, RG-202012-00245), and the Lady Tata Memorial Trust (International Award for Research in Leukaemia 2021-2022, LADY_TATA_21_3223); the Hellenic Precision Medicine Network in Oncology; project ODYSSEAS (Intelligent and Automated Systems for enabling the Design, Simulation and Development of Integrated Processes and Products) implemented under the “Action for the Strategic Development on the Research and Technological Sector”, funded by the Operational Programme “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020) and co-financed by Greece and the European Union, with grant agreement no: MIS 5002462”; MH CZ—DRO (FNBr, 65269705), NV19-03-00091 and the project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102)—Funded by the European Union—Next-Generation EU; Instituto de Salud Carlos III (ISCIII), “PI21/00983”, co-funded by the European Union; the EU’s Horizon 2020 research and innovation program under grant agreement No. 739593, by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the K21_137948, FK20_134253, TKP2021-EGA-24 and TKP2021-NVA-15 funding schemes, and Elixir Hungary; Instituto de Salud Carlos III (ISCIII), “PI21/00983”, co-funded by the European Union; Fondo di Ateneo per la Ricerca (FAR) 2019, 2020 and 2021 of the University of Ferrara (GMR; AC), Associazione Italiana contro le Leucemie-Linfomi e Mieloma ONLUS Ferrara (AC; GMR), BEAT Leukemia Foundation Milan Italy (AC); the Danish Cancer Society and the CLL-CLUE project under the frame of ERA PerMed; Cancer Research UK (ECRIN-M3 accelerator award C42023/A29370, Southampton Experimental Cancer Medicine Centre grant C24563/A15581, Cancer Research UK Southampton Centre grant C34999/A18087, and programme C2750/A23669); the Swedish Cancer Society (19 0425 Pj 01 H), the Swedish Research Council (2020-01750), the Knut and Alice Wallenberg Foundation (2016.0373), Region Stockholm (ALF/FoUI-962423), and Radiumhemmets Forskningsfonder (194133), Stockholm; and Lion’s Cancer Research Foundation, Uppsala.

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