TY - JOUR
TI - Cytogenetic complexity in chronic lymphocytic leukemia: Definitions, associations, and clinical impact
AU - Baliakas, P.
AU - Jeromin, S.
AU - Iskas, M.
AU - Puiggros, A.
AU - Plevova, K.
AU - Nguyen-Khac, F.
AU - Davis, Z.
AU - Matteo Rigolin, G.
AU - Visentin, A.
AU - Xochelli, A.
AU - Delgado, J.
AU - Baran-Marszak, F.
AU - Stalika, E.
AU - Abrisqueta, P.
AU - Durechova, K.
AU - Papaioannou, G.
AU - Eclache, V.
AU - DImou, M.
AU - Iliakis, T.
AU - Collado, R.
AU - Doubek, M.
AU - Calasanz, M.J.
AU - Ruiz-Xiville, N.
AU - Moreno, C.
AU - Jarosova, M.
AU - Leeksma, A.C.
AU - Panayiotidis, P.
AU - Podgornik, H.
AU - Cymbalista, F.
AU - Anagnostopoulos, A.
AU - Trentin, L.
AU - Stavroyianni, N.
AU - Davi, F.
AU - Ghia, P.
AU - Kater, A.P.
AU - Cuneo, A.
AU - Pospisilova, S.
AU - Espinet, B.
AU - Athanasiadou, A.
AU - Oscier, D.
AU - Haferlach, C.
AU - Stamatopoulos, K.
AU - on behalf of ERIC, the European Research Initiative on CLL
JO - Blood advances
PY - 2019
VL - 133
TODO - 11
SP - 1205-1216
PB - American Society of Hematology
SN - null
TODO - 10.1182/blood-2018-09-873083
TODO - 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
TODO - 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.
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