Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status : a study by ERIC in HARMONY
Mansouri, Larry (Karolinska Institutet (Estocolm, Suècia))
Thorvaldsdottir, Birna (Karolinska Institutet (Estocolm, Suècia))
Sutton, Lesley-Ann (Karolinska Institutet (Estocolm, Suècia))
Karakatsoulis, Georgios (University of Ioannina. Department of Mathematics)
Meggendorfer, Manja (MLL Munich Leukemia Laboratory)
Parker, Helen (University of Southampton)
Nadeu, Ferran (Centro de Investigación Biomédica en Red de Cáncer)
Brieghel, Christian (Copenhagen University Hospital. Department of Hematology, Rigshospitalet)
Laidou, Stamatia (Centre for Research and Technology Hellas (Tessalònica, Grècia))
Moia, Riccardo (Università del Piemonte Orientale)
Rossi, Davide (Institute of Oncology Research (Suïssa))
Catherwood, Mark (Queen's University Belfast)
Kotaskova, Jana (Masaryk University)
Delgado, Julio (Universitat de Barcelona)
Rodríguez-Vicente, Ana E. (Hospital Universitario de Salamanca)
Benito, Rocío (Hospital Universitario de Salamanca)
Rigolin, Gian Matteo (University of Ferrara)
Bonfiglio, Silvia (Università Vita Salute San Raffaele and IRCCS Ospedale San Raffaele)
Scarfo, Lydia (Università Vita Salute San Raffaele)
Mattsson, Mattias (Uppsala University. Department of Immunology, Genetics and Pathology)
Davis, Zadie (Molecular Pathology Department, University Hospitals Dorset)
Gogia, Ajay (All India Institute of Medical Sciences (Nova Delhi, Índia))
Rani, Lata (All India Institute of Medical Sciences (Nova Delhi, Índia))
Baliakas, Panagiotis (Uppsala University. Department of Immunology, Genetics and Pathology)
Foroughi-Asl, Hassan (Karolinska Institutet (Estocolm, Suècia))
Jylhä, Cecilia (Karolinska Institutet (Estocolm, Suècia))
Skaftason, Aron (Karolinska Institutet (Estocolm, Suècia))
Rapado, Inmaculada (Spanish National Cancer Research)
Miras, Fatima (Hospital Universitario 12 de Octubre (Madrid))
Martinez-Lopez, Joaquín (Spanish National Cancer Research)
de la Serna, Javier (Spanish National Cancer Research)
Rivas, Jesús María Hernández (Hospital Universitario de Salamanca)
Thornton, Patrick (Beaumont Hospital (Dublín, Irlanda))
Larráyoz, María José (Instituto de Investigación Sanitaria de Navarra)
Calasanz, M.J (Instituto de Investigación Sanitaria de Navarra)
Fésüs, Viktória (Semmelweis University)
Mátrai, Zoltán (Central Hospital of Southern Pest-National Institute of Hematology and Infectious Diseases, Budapest, Hungary)
Bödör, Csaba (Semmelweis University)
Smedby, Karin E. (Karolinska Institutet (Suècia). Department of Medicine Solna)
Espinet, Blanca (Institut Hospital del Mar d'Investigacions Mèdiques)
Puiggros, Anna (Institut Hospital del Mar d'Investigacions Mèdiques)
Gupta, Ritu (All India Institute of Medical Sciences (Nova Delhi, Índia))
Bullinger, Lars (Charité - Universitätsmedizin Berlin)
Bosch José, Francesc Xavier 1947- (Vall d'Hebron Institut d'Oncologia)
Tazón-Vega, Bárbara (Vall d'Hebron Institut d'Oncologia)
Baran-Marszak, Fanny (Service d'hématologie Biologique Hôpital Avicenne Assistance Publique des Hôpitaux de Paris)
Oscier, David (University Hospitals Dorset)
Nguyen-Khac, Florence (Sorbonne University)
Zenz, Thorsten (University Hospital and University of Zurich. Department of Oncology and Haematology)
Terol, Maria Jose (University of Valencia. Department of Hematology)
Cuneo, Antonio (University of Ferrara. Hematology-Department of Medical Sciences)
Hernández-Sánchez, María (Hospital Universitario de Salamanca)
Pospisilova, Sarka (Masaryk University. Central European Institute of Technology)
Mills, Ken (Queen's University Belfast)
Gaidano, Gianluca (Università del Piemonte Orientale)
Niemann, Carsten U. (Copenhagen University Hospital)
Campo, Elias (Universitat de Barcelona)
Strefford, Jonathan C. (University of Southampton)
Ghia, Paolo (Università Vita Salute San Raffaele and IRCCS Ospedale San Raffaele)
Stamatopoulos, Kostas (Institute of Applied Biosciences (Grècia))
Rosenquist, Richard (Karolinska University Hospital and Karolinska Institutet (Suècia))
Universitat Autònoma de Barcelona

Data:	2022
Resum:	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.
Ajuts:	"la Caixa" Foundation HR17-00221
Nota:	Altres ajuts; Cancerfonden (Swedish Cancer Society) 19 0425 Pj 01 H ; Vetenskapsrådet (Swedish Research Council) 2020-01750 ; Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation) 2016.0373
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cancer genetics ; Genetics research
Publicat a:	Leukemia, Vol. 37 (december 2022) , p. 339-347, ISSN 1476-5551

DOI: 10.1038/s41375-022-01802-y
PMID: 36566271

9 p, 1.7 MB

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