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

  • Panagiotis Baliakas
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
  • Sabine Jeromin
    MLL Munich Leukemia Laboratory, Munich, Germany;
  • Michalis Iskas
    Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece;
  • Anna Puiggros
    Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain;
  • Karla Plevova
    Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic;
  • Florence Nguyen-Khac
    Hematology Department and Sorbonne University, Hopital Pitie-Salpetriere, INSERM U1138, Paris, France;
  • Zadie Davis
    Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom;
  • Gian Matteo Rigolin
    Hematology Section, St. Anna University Hospital, Ferrara, Italy;
  • Andrea Visentin
    Hematology Division, Department of Medicine, University of Padua, Padua, Italy;
  • Aliki Xochelli
    Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece;
  • Julio Delgado
    Department of Hematology, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain;
  • Fanny Baran-Marszak
    Laboratoire d’hématologie, Hopital Avicenne, Assistance Publique–Hôpitaux de Paris, Paris, France;
  • Evangelia Stalika
    Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece;
  • Pau Abrisqueta
    Servei d’Hematología, Hospital Vall d'Hebron, Barcelona, Spain;
  • Kristina Durechova
    Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic;
  • George Papaioannou
    Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece;
  • Virginie Eclache
    Laboratoire d’hématologie, Hopital Avicenne, Assistance Publique–Hôpitaux de Paris, Paris, France;
  • Maria Dimou
    Hematology Section, First Department of Propedeutic Internal Medicine, National and Kapodistrian University of Athens, Laikon University Hospital, Athens, Greece;
  • Theodoros Iliakis
    Hematology Section, First Department of Propedeutic Internal Medicine, National and Kapodistrian University of Athens, Laikon University Hospital, Athens, Greece;
  • Rosa Collado
    Servicio de Hematología, Consorcio Hospital General Universitario, Valencia, Spain;
  • Michael Doubek
    Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic;
  • M. Jose Calasanz
    Servicio de Genética Citogenética, Departamento de Genética, Universidad de Navarra, Pamplona, Spain;
  • 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;
  • Carolina Moreno
    Servei d’Hematologia, Hospital Universitari de la Santa Creu i Sant Pau, Barcelona, Spain;
  • Marie Jarosova
    Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic;
  • Alexander C. Leeksma
    Department of Hematology and Lymphoma and Myeloma Center Amsterdam, Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands;
  • Panayiotis Panayiotidis
    Hematology Section, First Department of Propedeutic Internal Medicine, National and Kapodistrian University of Athens, Laikon University Hospital, Athens, Greece;
  • Helena Podgornik
    Department of Hematology, University Medical Centre Ljubljana, Ljubljana, Slovenia; and
  • Florence Cymbalista
    Laboratoire d’hématologie, Hopital Avicenne, Assistance Publique–Hôpitaux de Paris, Paris, France;
  • Achilles Anagnostopoulos
    Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece;
  • Livio Trentin
    Hematology Division, Department of Medicine, University of Padua, Padua, Italy;
  • Niki Stavroyianni
    Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece;
  • Fred Davi
    Hematology Department and Sorbonne University, Hopital Pitie-Salpetriere, INSERM U1138, Paris, France;
  • Paolo Ghia
    Strategic Research Program in CLL, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute and Università Vita-Salute San Raffaele, Milan, Italy
  • Arnon P. Kater
    Department of Hematology and Lymphoma and Myeloma Center Amsterdam, Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands;
  • Antonio Cuneo
    Hematology Section, St. Anna University Hospital, Ferrara, Italy;
  • Sarka Pospisilova
    Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic;
  • Blanca Espinet
    Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain;
  • Anastasia Athanasiadou
    Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece;
  • David Oscier
    Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom;
  • Claudia Haferlach
    MLL Munich Leukemia Laboratory, Munich, Germany;
  • 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

  • Blood

    Blood 133 (11), 1205-1216, 2019-03-14

    American Society of Hematology

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