Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact.

Autor:	Baliakas P; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Jeromin S; MLL Munich Leukemia Laboratory, Munich, Germany., Iskas M; Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece., Puiggros A; Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain.; Grup de Recerca Translacional en Neoplàsies Hematològiques, Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain., Plevova K; Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic.; Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic., Nguyen-Khac F; Hematology Department and Sorbonne University, Hopital Pitie-Salpetriere, INSERM U1138, Paris, France., Davis Z; Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom., Rigolin GM; Hematology Section, St. Anna University Hospital, Ferrara, Italy., Visentin A; Hematology Division, Department of Medicine, University of Padua, Padua, Italy., Xochelli A; Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece., Delgado J; Department of Hematology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain., Baran-Marszak F; Laboratoire d'hématologie, Hopital Avicenne, Assistance Publique-Hôpitaux de Paris, Paris, France., Stalika E; Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece., Abrisqueta P; Servei d'Hematología, Hospital Vall d'Hebron, Barcelona, Spain., Durechova K; Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic., Papaioannou G; Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece., Eclache V; Laboratoire d'hématologie, Hopital Avicenne, Assistance Publique-Hôpitaux de Paris, Paris, France., Dimou M; Hematology Section, First Department of Propedeutic Internal Medicine, National and Kapodistrian University of Athens, Laikon University Hospital, Athens, Greece., Iliakis T; Hematology Section, First Department of Propedeutic Internal Medicine, National and Kapodistrian University of Athens, Laikon University Hospital, Athens, Greece., Collado R; Servicio de Hematología, Consorcio Hospital General Universitario, Valencia, Spain., Doubek M; Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic.; Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic., Calasanz MJ; Servicio de Genética Citogenética, Departamento de Genética, Universidad de Navarra, Pamplona, Spain., Ruiz-Xiville N; Servei Laboratori Hematologia, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona, Badalona, Spain., Moreno C; Servei d'Hematologia, Hospital Universitari de la Santa Creu i Sant Pau, Barcelona, Spain., Jarosova M; Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic.; Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic., Leeksma AC; Department of Hematology and Lymphoma and Myeloma Center Amsterdam, Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.; Department of Experimental Immunology, Cancer Center Amsterdam and Infection and Immunity Institute of Amsterdam, Amsterdam, The Netherlands., Panayiotidis P; Hematology Section, First Department of Propedeutic Internal Medicine, National and Kapodistrian University of Athens, Laikon University Hospital, Athens, Greece., Podgornik H; Department of Hematology, University Medical Centre Ljubljana, Ljubljana, Slovenia; and., Cymbalista F; Laboratoire d'hématologie, Hopital Avicenne, Assistance Publique-Hôpitaux de Paris, Paris, France., Anagnostopoulos A; Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece., Trentin L; Hematology Division, Department of Medicine, University of Padua, Padua, Italy., Stavroyianni N; Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece., Davi F; Hematology Department and Sorbonne University, Hopital Pitie-Salpetriere, INSERM U1138, Paris, France., Ghia P; Strategic Research Program in CLL, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute and Università Vita-Salute San Raffaele, Milan, Italy., Kater AP; Department of Hematology and Lymphoma and Myeloma Center Amsterdam, Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.; Department of Experimental Immunology, Cancer Center Amsterdam and Infection and Immunity Institute of Amsterdam, Amsterdam, The Netherlands., Cuneo A; Hematology Section, St. Anna University Hospital, Ferrara, Italy., Pospisilova S; Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic.; Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic., Espinet B; Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain.; Grup de Recerca Translacional en Neoplàsies Hematològiques, Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain., Athanasiadou A; Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece., Oscier D; Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom., Haferlach C; MLL Munich Leukemia Laboratory, Munich, Germany., Stamatopoulos K; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.; Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2019 Mar 14; Vol. 133 (11), pp. 1205-1216. Date of Electronic Publication: 2019 Jan 02.
DOI:	10.1182/blood-2018-09-873083
Abstrakt:	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 [ TP53 abs]), 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 TP53 abs. At the other end of the spectrum, patients with CK and +12,+19 displayed an exceptionally indolent profile. Building upon CK, TP53 abs, 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 TP53 abs, 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. (© 2019 by The American Society of Hematology.)
Databáze:	MEDLINE
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