Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multi-center study.
Détails
Télécharger: 31974198_BIB_66A0549DE1D2.pdf (1482.91 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY-NC 4.0
Etat: Public
Version: Final published version
Licence: CC BY-NC 4.0
ID Serval
serval:BIB_66A0549DE1D2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multi-center study.
Périodique
Haematologica
ISSN
1592-8721 (Electronic)
ISSN-L
0390-6078
Statut éditorial
Publié
Date de publication
01/01/2021
Peer-reviewed
Oui
Volume
106
Numéro
1
Pages
87-97
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Complex karyotype (CK) identified by chromosome-banding analysis (CBA) has shown prognostic value in chronic lymphocytic leukemia (CLL). Genomic arrays offer high-resolution genome-wide detection of copy-number alterations (CNAs) and could therefore be well equipped to detect the presence of a CK. Current knowledge on genomic arrays in CLL is based on outcomes of single center studies, in which different cutoffs for CNA calling were used. To further determine the clinical utility of genomic arrays for CNA assessment in CLL diagnostics, we retrospectively analyzed 2293 arrays from 13 diagnostic laboratories according to established standards. CNAs were found outside regions captured by CLL FISH probes in 34% of patients, and several of them including gains of 8q, deletions of 9p and 18p (p<0.01) were linked to poor outcome after correction for multiple testing. Patients (n=972) could be divided in three distinct prognostic subgroups based on the number of CNAs. Only high genomic complexity (high-GC), defined as ≥5 CNAs emerged as an independent adverse prognosticator on multivariable analysis for time to first treatment (Hazard ratio: 2.15, 95% CI: 1.36-3.41; p=0.001) and overall survival (Hazard ratio: 2.54, 95% CI: 1.54-4.17; p<0.001; n=528). Lowering the size cutoff to 1 Mb in 647 patients did not significantly improve risk assessment. Genomic arrays detected more chromosomal abnormalities and performed at least as well in terms of risk stratification compared to simultaneous chromosome banding analysis as determined in 122 patients. Our findings highlight genomic array as an accurate tool for CLL risk stratification.
Mots-clé
Chronic Lymphocytic Leukemia, Cytogenetics and Molecular Genetics, Genomic complexity, Lymphoproliferative Disorders
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/01/2020 16:39
Dernière modification de la notice
23/11/2022 7:11