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

Autor: Mansouri L; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden., Thorvaldsdottir B; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden., 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., Nadeu F; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain., Brieghel C; Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Laidou S; Centre for Research and Technology Hellas, Institute of Applied Biosciences, Thessaloniki, Greece., Moia R; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Rossi D; Division of Hematology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.; Laboratory of Experimental Hematology, Institute of Oncology Research, Bellinzona, Switzerland., Catherwood M; Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK., Kotaskova J; Department of Internal Medicine-Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.; Faculty of Medicine, Masaryk University, Brno, Czech Republic.; Central European Institute of Technology, Masaryk University, Brno, Czech Republic., Delgado J; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.; Hospital Clínic of Barcelona, Barcelona, Spain.; Universitat de Barcelona, Barcelona, Spain., Rodríguez-Vicente AE; Cancer Research Center (IBMCC) CSIC-University of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica (IBSAL), Salamanca, Spain.; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain., Benito R; Cancer Research Center (IBMCC) CSIC-University of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica (IBSAL), Salamanca, Spain.; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain., Rigolin GM; Hematology-Department of Medical Sciences, University of Ferrara, Ferrara, Italy., Bonfiglio S; Università Vita Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano, Italy., Scarfo L; Università Vita Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano, Italy., Mattsson M; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden., Davis Z; Molecular Pathology Department, University Hospitals Dorset, Bournemouth, UK., Gogia A; All India Institute of Medical Sciences (AIIMS), New Delhi, India., Rani L; All India Institute of Medical Sciences (AIIMS), New Delhi, India., Baliakas P; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden., Foroughi-Asl H; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden., Jylhä C; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden., Skaftason A; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden., Rapado I; Hospital Universitario 12 Octubre, Madrid, Spain.; Spanish National Cancer Research (CNIO), Madrid, Spain., Miras F; Hospital Universitario 12 Octubre, Madrid, Spain., Martinez-Lopez J; Hospital Universitario 12 Octubre, Madrid, Spain.; Spanish National Cancer Research (CNIO), Madrid, Spain., de la Serna J; Hospital Universitario 12 Octubre, Madrid, Spain.; Spanish National Cancer Research (CNIO), Madrid, Spain., Rivas JMH; Cancer Research Center (IBMCC) CSIC-University of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica (IBSAL), Salamanca, Spain.; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain., Thornton P; Haematology Department, Beaumont Hospital, Dublin, Ireland., Larráyoz MJ; Hematological Diseases Laboratory, CIMA LAB Diagnostics, University of Navarra, Pamplona, Spain.; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain., Calasanz MJ; Hematological Diseases Laboratory, CIMA LAB Diagnostics, University of Navarra, Pamplona, Spain.; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain., Fésüs V; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary., Mátrai Z; Central Hospital of Southern Pest-National Institute of Hematology and Infectious Diseases, Budapest, Hungary., Bödör C; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary., Smedby KE; Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden., Espinet B; Molecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar and Translational Research on Hematological Neoplasms Group, Hospital del Mar Research Institute (IMIM), Barcelona, Spain., Puiggros A; Molecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar and Translational Research on Hematological Neoplasms Group, Hospital del Mar Research Institute (IMIM), Barcelona, Spain., Gupta R; All India Institute of Medical Sciences (AIIMS), New Delhi, India., Bullinger L; Department of Hematology, Oncology and Cancer Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany., Bosch F; Department of Hematology, Hospital Universitari Vall d'Hebron (HUVH), Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain., Tazón-Vega B; Department of Hematology, Hospital Universitari Vall d'Hebron (HUVH), Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain., Baran-Marszak F; Service d'hématologie Biologique Hôpital Avicenne Assistance Publique des Hôpitaux de Paris, Bobigny, France., Oscier D; Molecular Pathology Department, University Hospitals Dorset, Bournemouth, UK., Nguyen-Khac F; Sorbonne Université, Service d'Hématologie Clinique, Hôpital Pitié-Salpêtrière, APHP, Paris, France., Zenz T; Department of Oncology and Haematology, University Hospital and University of Zurich, Zurich, Switzerland., Terol MJ; Department of Hematology, INCLIVA Research Insitute, University of Valencia, Valencia, Spain., Cuneo A; Hematology-Department of Medical Sciences, University of Ferrara, Ferrara, Italy., Hernández-Sánchez M; Cancer Research Center (IBMCC) CSIC-University of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica (IBSAL), Salamanca, Spain.; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain., Pospisilova S; Department of Internal Medicine-Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.; Faculty of Medicine, Masaryk University, Brno, Czech Republic.; Central European Institute of Technology, Masaryk University, Brno, Czech Republic., Mills K; Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK., Gaidano G; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Niemann CU; Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Campo E; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.; Hospital Clínic of Barcelona, Barcelona, Spain.; Universitat de Barcelona, Barcelona, Spain., Strefford JC; Cancer Genomics, School for Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK., Ghia P; Università Vita Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano, Italy., Stamatopoulos K; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.; Centre for Research and Technology Hellas, Institute of Applied Biosciences, Thessaloniki, Greece., Rosenquist R; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. richard.rosenquist@ki.se.; Clinical Genetics, Karolinska University Hospital, Solna, Sweden. richard.rosenquist@ki.se.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2023 Feb; Vol. 37 (2), pp. 339-347. Date of Electronic Publication: 2022 Dec 24.
DOI: 10.1038/s41375-022-01802-y
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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