15 results on '"Rossi, Davide"'
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2. ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia—2024 update
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Malcikova, Jitka, Pavlova, Sarka, Baliakas, Panagiotis, Chatzikonstantinou, Thomas, Tausch, Eugen, Catherwood, Mark, Rossi, Davide, Soussi, Thierry, Tichy, Boris, Kater, Arnon P., Niemann, Carsten U., Davi, Frederic, Gaidano, Gianluca, Stilgenbauer, Stephan, Rosenquist, Richard, Stamatopoulos, Kostas, Ghia, Paolo, and Pospisilova, Sarka
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- 2024
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3. Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY
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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
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- 2023
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4. Measurable residual disease in chronic lymphocytic leukemia: expert review and consensus recommendations
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Wierda, William G., Rawstron, Andrew, Cymbalista, Florence, Badoux, Xavier, Rossi, Davide, Brown, Jennifer R., Egle, Alexander, Abello, Virginia, Cervera Ceballos, Eduardo, Herishanu, Yair, Mulligan, Stephen P., Niemann, Carsten U., Diong, Colin P., Soysal, Teoman, Suzuki, Ritsuro, Tran, Hoa T. T., Wu, Shang-Ju, Owen, Carolyn, Stilgenbauer, Stephan, Ghia, Paolo, and Hillmen, Peter
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- 2021
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5. Lymphocyte doubling time in chronic lymphocytic leukemia modern era: a real-life study in 848 unselected patients
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Baumann, Tycho, Moia, Riccardo, Gaidano, Gianluca, Delgado, Julio, Condoluci, Adalgisa, Villamor, Neus, Payedimarri, Anil Babu, Costa, Dolors, Patriarca, Andrea, Jiménez-Vicente, Carlos, Rossi, Davide, and Montserrat, Emili
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- 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
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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
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- 2023
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7. Survival risk score for real-life relapsed/refractory chronic lymphocytic leukemia patients receiving ibrutinib. A campus CLL study
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Gentile, Massimo, Morabito, Fortunato, Del Poeta, Giovanni, Mauro, Francesca Romana, Reda, Gianluigi, Sportoletti, Paolo, Laurenti, Luca, Coscia, Marta, Herishanu, Yair, Recchia, Anna Grazia, Varettoni, Marzia, Murru, Roberta, Chiarenza, Annalisa, Condoluci, Adalgisa, Moia, Riccardo, Pietrasanta, Daniela, Loseto, Giacomo, Consoli, Ugo, Scortechini, Ilaria, Rossi, Francesca Maria, Zucchetto, Antonella, Fraticelli, Vincenzo, Vigna, Ernesto, Botta, Cirino, Tripepi, Giovanni, Arrigo, Graziella D’, Rago, Angela, Angeletti, Ilaria, Biagi, Annalisa, Del Giudice, Ilaria, Bomben, Riccardo, Rigolin, Gian Matteo, Rossi, Davide, Di Raimondo, Francesco, Gaidano, Gianluca, Polliack, Aaron, Cuneo, Antonio, Foà, Robin, and Gattei, Valter
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- 2021
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8. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus
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Scarfò, Lydia, Chatzikonstantinou, Thomas, Rigolin, Gian Matteo, Quaresmini, Giulia, Motta, Marina, Vitale, Candida, Garcia-Marco, Jose Antonio, Hernández-Rivas, José Ángel, Mirás, Fatima, Baile, Mónica, Marquet, Juan, Niemann, Carsten U., Reda, Gianluigi, Munir, Talha, Gimeno, Eva, Marchetti, Monia, Quaglia, Francesca Maria, Varettoni, Marzia, Delgado, Julio, Iyengar, Sunil, Janssens, Ann, Marasca, Roberto, Ferrari, Angela, Cuéllar-García, Carolina, Itchaki, Gilad, Špaček, Martin, De Paoli, Lorenzo, Laurenti, Luca, Levin, Mark-David, Lista, Enrico, Mauro, Francesca R., Šimkovič, Martin, Van Der Spek, Ellen, Vandenberghe, Elisabeth, Trentin, Livio, Wasik-Szczepanek, Ewa, Ruchlemer, Rosa, Bron, Dominique, De Paolis, Maria Rosaria, Del Poeta, Giovanni, Farina, Lucia, Foglietta, Myriam, Gentile, Massimo, Herishanu, Yair, Herold, Tobias, Jaksic, Ozren, Kater, Arnon P., Kersting, Sabina, Malerba, Lara, Orsucci, Lorella, Popov, Viola Maria, Sportoletti, Paolo, Yassin, Mohamed, Pocali, Barbara, Barna, Gabor, Chiarenza, Annalisa, dos Santos, Gimena, Nikitin, Eugene, Andres, Martin, Dimou, Maria, Doubek, Michael, Enrico, Alicia, Hakobyan, Yervand, Kalashnikova, Olga, Ortiz Pareja, Macarena, Papaioannou, Maria, Rossi, Davide, Shah, Nimish, Shrestha, Amit, Stanca, Oana, Stavroyianni, Niki, Strugov, Vladimir, Tam, Constantine, Zdrenghea, Mihnea, Coscia, Marta, Stamatopoulos, Kostas, Rossi, Giuseppe, Rambaldi, Alessandro, Montserrat, Emili’, Foà, Robin, Cuneo, Antonio, and Ghia, Paolo
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- 2020
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9. Different time-dependent changes of risk for evolution in chronic lymphocytic leukemia with mutated or unmutated antigen B cell receptors
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Moysiadis, Theodoros, Baliakas, Panagiotis, Rossi, Davide, Catherwood, Mark, Strefford, Jonathan C., Delgado, Julio, Anagnostopoulos, Achilles, Belessi, Chrysoula, Stavroyianni, Niki, Pospisilova, Sarka, Oscier, David, Gaidano, Gianluca, Campo, Elias, Rosenquist, Richard, Ghia, Paolo, and Stamatopoulos, Kostas
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- 2019
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10. The VLA-4 integrin is constitutively active in circulating chronic lymphocytic leukemia cells via BCR autonomous signaling: a novel anchor-independent mechanism exploiting soluble blood-borne ligands
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Tissino, Erika, Gaglio, Annalisa, Nicolò, Antonella, Pozzo, Federico, Bittolo, Tamara, Rossi, Francesca Maria, Bomben, Riccardo, Nanni, Paola, Cattarossi, Ilaria, Zaina, Eva, Zimbo, Anna Maria, Ianna, Giulia, Capasso, Guido, Forestieri, Gabriela, Moia, Riccardo, Datta, Moumita, Härzschel, Andrea, Olivieri, Jacopo, D’Arena, Giovanni, Laurenti, Luca, Zaja, Francesco, Chiarenza, Annalisa, Palumbo, Giuseppe A., Martino, Enrica Antonia, Gentile, Massimo, Rossi, Davide, Gaidano, Gianluca, Del Poeta, Giovanni, Laureana, Roberta, Del Principe, Maria Ilaria, Maity, Palash C., Jumaa, Hassan, Hartmann, Tanja Nicole, Zucchetto, Antonella, and Gattei, Valter
- Abstract
In chronic lymphocytic leukemia (CLL), survival of neoplastic cells depends on microenvironmental signals at lymphoid sites where the crosstalk between the integrin VLA-4 (CD49d/CD29), expressed in ~40% of CLL, and the B-cell receptor (BCR) occurs. Here, BCR engagement inside–out activates VLA-4, thus enhancing VLA-4-mediated adhesion of CLL cells, which in turn obtain pro-survival signals from the surrounding microenvironment. We report that the BCR is also able to effectively inside–out activate the VLA-4 integrin in circulating CD49d-expressing CLL cells through an autonomous antigen-independent BCR signaling. As a consequence, circulating CLL cells exhibiting activated VLA-4 express markers of BCR pathway activation (phospho-BTK and phospho-PLC-γ2) along with higher levels of phospho-ERK and phospho-AKT indicating parallel activation of downstream pathways. Moreover, circulating CLL cells expressing activated VLA-4 bind soluble blood-borne VCAM-1 leading to increased VLA-4-dependent actin polymerization/re-organization and ERK phosphorylation. Finally, evidence is provided that ibrutinib treatment, by affecting autonomous BCR signaling, impairs the constitutive VLA-4 activation eventually decreasing soluble VCAM-1 binding and reducing downstream ERK phosphorylation by circulating CLL cells. This study describes a novel anchor-independent mechanism occurring in circulating CLL cells involving the BCR and the VLA-4 integrin, which help to unravel the peculiar biological and clinical features of CD49d+ CLL.
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- 2024
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11. ERIC recommendations for TP53mutation analysis in chronic lymphocytic leukemia—2024 update
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Malcikova, Jitka, Pavlova, Sarka, Baliakas, Panagiotis, Chatzikonstantinou, Thomas, Tausch, Eugen, Catherwood, Mark, Rossi, Davide, Soussi, Thierry, Tichy, Boris, Kater, Arnon P., Niemann, Carsten U., Davi, Frederic, Gaidano, Gianluca, Stilgenbauer, Stephan, Rosenquist, Richard, Stamatopoulos, Kostas, Ghia, Paolo, and Pospisilova, Sarka
- Abstract
In chronic lymphocytic leukemia (CLL), analysis of TP53aberrations (deletion and/or mutation) is a crucial part of treatment decision-making algorithms. Technological and treatment advances have resulted in the need for an update of the last recommendations for TP53analysis in CLL, published by ERIC, the European Research Initiative on CLL, in 2018. Based on the current knowledge of the relevance of low-burden TP53-mutated clones, a specific variant allele frequency (VAF) cut-off for reporting TP53mutations is no longer recommended, but instead, the need for thorough method validation by the reporting laboratory is emphasized. The result of TP53analyses should always be interpreted within the context of available laboratory and clinical information, treatment indication, and therapeutic options. Methodological aspects of introducing next-generation sequencing (NGS) in routine practice are discussed with a focus on reliable detection of low-burden clones. Furthermore, potential interpretation challenges are presented, and a simplified algorithm for the classification of TP53variants in CLL is provided, representing a consensus based on previously published guidelines. Finally, the reporting requirements are highlighted, including a template for clinical reports of TP53aberrations. These recommendations are intended to assist diagnosticians in the correct assessment of TP53mutation status, but also physicians in the appropriate understanding of the lab reports, thus decreasing the risk of misinterpretation and incorrect management of patients in routine practice whilst also leading to improved stratification of patients with CLL in clinical trials.
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- 2024
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12. Validation of a biological score to predict response in chronic lymphocytic leukemia patients treated front-line with bendamustine and rituximab
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Gentile, Massimo, Shanafelt, Tait D., Reda, Gianluigi, Mauro, Francesca Romana, Zirlik, Katja, Ciolli, Stefania, Laurenti, Luca, Del Principe, Maria Ilaria, Rossi, Davide, Di Renzo, Nicola, Molica, Stefano, Angrilli, Francesco, Coscia, Marta, Chiarenza, Annalisa, Giordano, Annamaria, Cutrona, Giovanna, Chaffee, Kari G., Parikh, Sameer A., Uccello, Giuseppina, Innocenti, Idanna, Tripepi, Giovanni, D’Arrigo, Graziella, Vigna, Ernesto, Recchia, Anna Grazia, Herishanu, Yair, Shvidel, Lev, Tadmor, Tamar, Cortelezzi, Agostino, Del Poeta, Giovanni, Gaidano, Gianluca, Di Raimondo, Francesco, Neri, Antonino, Ferrarini, Manlio, Foà, Robin, Polliack, Aaron, and Morabito, Fortunato
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- 2018
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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
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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
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- 2022
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14. Survival risk score for real-life relapsed/refractory chronic lymphocytic leukemia patients receiving ibrutinib. A campus CLL study
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Gentile, Massimo, primary, Morabito, Fortunato, additional, Del Poeta, Giovanni, additional, Mauro, Francesca Romana, additional, Reda, Gianluigi, additional, Sportoletti, Paolo, additional, Laurenti, Luca, additional, Coscia, Marta, additional, Herishanu, Yair, additional, Recchia, Anna Grazia, additional, Varettoni, Marzia, additional, Murru, Roberta, additional, Chiarenza, Annalisa, additional, Condoluci, Adalgisa, additional, Moia, Riccardo, additional, Pietrasanta, Daniela, additional, Loseto, Giacomo, additional, Consoli, Ugo, additional, Scortechini, Ilaria, additional, Rossi, Francesca Maria, additional, Zucchetto, Antonella, additional, Fraticelli, Vincenzo, additional, Vigna, Ernesto, additional, Botta, Cirino, additional, Tripepi, Giovanni, additional, Arrigo, Graziella D’, additional, Rago, Angela, additional, Angeletti, Ilaria, additional, Biagi, Annalisa, additional, Del Giudice, Ilaria, additional, Bomben, Riccardo, additional, Rigolin, Gian Matteo, additional, Rossi, Davide, additional, Di Raimondo, Francesco, additional, Gaidano, Gianluca, additional, Polliack, Aaron, additional, Cuneo, Antonio, additional, Foà, Robin, additional, and Gattei, Valter, additional
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- 2020
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15. Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY
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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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