@article{3000561,
    title = "Cytogenetic complexity in chronic lymphocytic leukemia: Definitions, associations, and clinical impact",
    author = "Baliakas, P. and Jeromin, S. and Iskas, M. and Puiggros, A. and Plevova, K. and Nguyen-Khac, F. and Davis, Z. and Matteo Rigolin, G. and Visentin, A. and Xochelli, A. and Delgado, J. and Baran-Marszak, F. and Stalika, E. and Abrisqueta, P. and Durechova, K. and Papaioannou, G. and Eclache, V. and DImou, M. and Iliakis, T. and Collado, R. and Doubek, M. and Calasanz, M.J. and Ruiz-Xiville, N. and Moreno, C. and Jarosova, M. and Leeksma, A.C. and Panayiotidis, P. and Podgornik, H. and Cymbalista, F. and Anagnostopoulos, A. and Trentin, L. and Stavroyianni, N. and Davi, F. and Ghia, P. and Kater, A.P. and Cuneo, A. and Pospisilova, S. and Espinet, B. and Athanasiadou, A. and Oscier, D. and Haferlach, C. and Stamatopoulos, K. and on behalf of ERIC, the European Research Initiative on CLL",
    journal = "Blood advances",
    year = "2019",
    volume = "133",
    number = "11",
    pages = "1205-1216",
    publisher = "American Society of Hematology",
    doi = "10.1182/blood-2018-09-873083",
    keywords = "B lymphocyte receptor;  protein p53;  protein p53;  TP53 protein, human;  tumor marker, adult;  Article;  cancer patient;  cancer survival;  chromosome 11q;  chromosome 17p;  chromosome aberration;  chromosome analysis;  chromosome deletion;  chronic lymphatic leukemia;  clinical outcome;  cytogenetics;  disease course;  exon;  female;  fluorescence in situ hybridization;  gene mutation;  genetic association;  genetic background;  human;  human cell;  immunogenetics;  immunoglobulin heavy chain gene;  karyotype;  major clinical study;  male;  middle aged;  monoclonal b cell lymphocytosis;  multicenter study;  next generation sequencing;  overall survival;  prevalence;  priority journal;  prospective study;  retrospective study;  Sanger sequencing;  somatic hypermutation;  trisomy 12;  aged;  chromosome aberration;  chronic lymphatic leukemia;  follow up;  genetics;  mortality;  mutation;  pathology;  procedures;  prognosis;  survival rate, Aged;  Biomarkers, Tumor;  Chromosome Aberrations;  Cytogenetics;  Female;  Follow-Up Studies;  Humans;  Leukemia, Lymphocytic, Chronic, B-Cell;  Male;  Middle Aged;  Mutation;  Prognosis;  Retrospective Studies;  Somatic Hypermutation, Immunoglobulin;  Survival Rate;  Tumor Suppressor Protein p53",
    abstract = "Recent evidence suggests that complex karyotype (CK) defined by the presence of ≥3 chromosomal aberrations (structural and/or numerical) identified by using chromosomebanding 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. © 2019 by The American Society of Hematology."
}