Informace o publikaci

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

Autoři	BALIAKAS P. JEROMIN S. ISKAS M. PUIGGROS A. PLEVOVÁ Karla NGUYEN-KHAC F. DAVIS Z. RIGOLIN G.M. VISENTIN A. XOCHELLI A. DELGADO J. BARAN-MARSZAK F. STALIKA E. ABRISQUETA P. ĎURECHOVÁ Kristina PAPAIOANNOU G. ECLACHE V. DIMOU M. ILIAKIS T. COLLADO R. DOUBEK Michael CALASANZ M.J. RUIZ-XIVILLE N. MORENO C. JAROŠOVÁ Marie LEEKSMA A.C. PANAYIOTIDIS P. PODGORNIK H. CYMBALISTA F. ANAGNOSTOPOULOS A. TRENTIN L. STAVROYIANNI N. DAVI F. GHIA P. KATER A.P. CUNEO A. POSPÍŠILOVÁ Šárka ESPINET B. ATHANASIADOU A. OSCIER D. HAFERLACH C. STAMATOPOULOS K.
Rok publikování	2019
Druh	Článek v odborném periodiku
Časopis / Zdroj	Blood
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
www	http://www.bloodjournal.org/content/133/11/1205?sso-checked=true
Doi	http://dx.doi.org/10.1182/blood-2018-09-873083
Klíčová slova	HEALTH-ORGANIZATION CLASSIFICATION; CHROMOSOME-BANDING ANALYSIS; RISK GENOMIC ABERRATIONS; IN-SITU HYBRIDIZATION; CLL PATIENTS; CONVENTIONAL CYTOGENETICS; CLONAL EVOLUTION; RECURRENT MUTATIONS; CPG OLIGONUCLEOTIDE; PROGNOSTIC INDEX
Popis	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 112,119 displayed an exceptionally indolent profile. Building upon CK, TP53abs, and immunoglobulin heavy variable gene somatic hyper-mutation 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 112,119, 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.
Související projekty:	Vliv selekce genomických poškození na průběh chronické lymfocytární leukémie Analýza klonální heterogenity chronické lymfocytární leukemie pomoci sekvenování nové generace genu pro B-buněčný receptor. Národní studie