Περίληψη:
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.
Συγγραφείς:
Baliakas, P.
Jeromin, S.
Iskas, M.
Puiggros, A.
Plevova, K.
Nguyen-Khac, F.
Davis, Z.
Matteo Rigolin, G.
Visentin, A.
Xochelli, A.
Delgado, J.
Baran-Marszak, F.
Stalika, E.
Abrisqueta, P.
Durechova, K.
Papaioannou, G.
Eclache, V.
DImou, M.
Iliakis, T.
Collado, R.
Doubek, M.
Calasanz, M.J.
Ruiz-Xiville, N.
Moreno, C.
Jarosova, M.
Leeksma, A.C.
Panayiotidis, P.
Podgornik, H.
Cymbalista, F.
Anagnostopoulos, A.
Trentin, L.
Stavroyianni, N.
Davi, F.
Ghia, P.
Kater, A.P.
Cuneo, A.
Pospisilova, S.
Espinet, B.
Athanasiadou, A.
Oscier, D.
Haferlach, C.
Stamatopoulos, K.
on behalf of ERIC, the European Research Initiative on CLL
Λέξεις-κλειδιά:
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
