Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact
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- Panagiotis Baliakas
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
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- Sabine Jeromin
- MLL Munich Leukemia Laboratory, Munich, Germany;
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- Michalis Iskas
- Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece;
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- Anna Puiggros
- Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain;
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- Karla Plevova
- Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic;
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- Florence Nguyen-Khac
- Hematology Department and Sorbonne University, Hopital Pitie-Salpetriere, INSERM U1138, Paris, France;
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- Zadie Davis
- Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom;
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- Gian Matteo Rigolin
- Hematology Section, St. Anna University Hospital, Ferrara, Italy;
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- Andrea Visentin
- Hematology Division, Department of Medicine, University of Padua, Padua, Italy;
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- Aliki Xochelli
- Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece;
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- Julio Delgado
- Department of Hematology, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain;
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- Fanny Baran-Marszak
- Laboratoire d’hématologie, Hopital Avicenne, Assistance Publique–Hôpitaux de Paris, Paris, France;
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- Evangelia Stalika
- Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece;
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- Pau Abrisqueta
- Servei d’Hematología, Hospital Vall d'Hebron, Barcelona, Spain;
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- Kristina Durechova
- Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic;
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- George Papaioannou
- Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece;
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- Virginie Eclache
- Laboratoire d’hématologie, Hopital Avicenne, Assistance Publique–Hôpitaux de Paris, Paris, France;
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- Maria Dimou
- Hematology Section, First Department of Propedeutic Internal Medicine, National and Kapodistrian University of Athens, Laikon University Hospital, Athens, Greece;
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- Theodoros Iliakis
- Hematology Section, First Department of Propedeutic Internal Medicine, National and Kapodistrian University of Athens, Laikon University Hospital, Athens, Greece;
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- Rosa Collado
- Servicio de Hematología, Consorcio Hospital General Universitario, Valencia, Spain;
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- Michael Doubek
- Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic;
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- M. Jose Calasanz
- Servicio de Genética Citogenética, Departamento de Genética, Universidad de Navarra, Pamplona, Spain;
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- Neus Ruiz-Xiville
- Servei Laboratori Hematologia, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona, Badalona, Spain;
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- Carolina Moreno
- Servei d’Hematologia, Hospital Universitari de la Santa Creu i Sant Pau, Barcelona, Spain;
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- Marie Jarosova
- Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic;
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- Alexander C. Leeksma
- Department of Hematology and Lymphoma and Myeloma Center Amsterdam, Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands;
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- Panayiotis Panayiotidis
- Hematology Section, First Department of Propedeutic Internal Medicine, National and Kapodistrian University of Athens, Laikon University Hospital, Athens, Greece;
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- Helena Podgornik
- Department of Hematology, University Medical Centre Ljubljana, Ljubljana, Slovenia; and
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- Florence Cymbalista
- Laboratoire d’hématologie, Hopital Avicenne, Assistance Publique–Hôpitaux de Paris, Paris, France;
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- Achilles Anagnostopoulos
- Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece;
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- Livio Trentin
- Hematology Division, Department of Medicine, University of Padua, Padua, Italy;
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- Niki Stavroyianni
- Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece;
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- Fred Davi
- Hematology Department and Sorbonne University, Hopital Pitie-Salpetriere, INSERM U1138, Paris, France;
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- Paolo Ghia
- Strategic Research Program in CLL, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute and Università Vita-Salute San Raffaele, Milan, Italy
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- Arnon P. Kater
- Department of Hematology and Lymphoma and Myeloma Center Amsterdam, Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands;
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- Antonio Cuneo
- Hematology Section, St. Anna University Hospital, Ferrara, Italy;
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- Sarka Pospisilova
- Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic;
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- Blanca Espinet
- Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain;
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- Anastasia Athanasiadou
- Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece;
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- David Oscier
- Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom;
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- Claudia Haferlach
- MLL Munich Leukemia Laboratory, Munich, Germany;
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- Kostas Stamatopoulos
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
抄録
<jats:title>Abstract</jats:title> <jats:p>Recent evidence suggests that complex karyotype (CK) defined by the presence of ≥3 chromosomal aberrations (structural and/or numerical) identified by using chromosome-banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges toward the routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with ≥5 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcomes, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and/or TP53 mutations [TP53abs]), and the expression of somatically hypermutated (M-CLL) or unmutated immunoglobulin heavy variable genes. Thus, they contrasted with CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53abs. At the other end of the spectrum, patients with CK and +12,+19 displayed an exceptionally indolent profile. Building upon CK, TP53abs, and immunoglobulin heavy variable gene somatic hypermutation status, we propose a novel hierarchical model in which patients with high-CK exhibit the worst prognosis, whereas those with mutated CLL lacking CK or TP53abs, as well as CK with +12,+19, show the longest overall survival. Thus, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with ≥5 chromosomal aberrations emerges as prognostically adverse, independent of other biomarkers. Prospective clinical validation is warranted before ultimately incorporating high-CK in risk stratification of CLL.</jats:p>
収録刊行物
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- Blood
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Blood 133 (11), 1205-1216, 2019-03-14
American Society of Hematology