Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multi-center study.

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Version: Final published version
License: CC BY-NC 4.0
Serval ID
serval:BIB_66A0549DE1D2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multi-center study.
Journal
Haematologica
Author(s)
Leeksma A.C., Baliakas P., Moysiadis T., Puiggros A., Plevova K., Van der Kevie-Kersemaekers A.M., Posthuma H., Rodriguez-Vicente A.E., Tran A.N., Barbany G., Mansouri L., Gunnarsson R., Parker H., Van den Berg E., Bellido M., Davis Z., Wall M., Scarpelli I., Österborg A., Hansson L., Jarosova M., Ghia P., Poddighe P., Espinet B., Pospisilova S., Tam C., Ysebaert L., Nguyen-Khac F., Oscier D., Haferlach C., Schoumans J., Stevens-Kroef M., Eldering E., Stamatopoulos K., Rosenquist R., Strefford J.C., Mellink C., Kater A.P.
ISSN
1592-8721 (Electronic)
ISSN-L
0390-6078
Publication state
Published
Issued date
01/01/2021
Peer-reviewed
Oui
Volume
106
Number
1
Pages
87-97
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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.
Keywords
Chronic Lymphocytic Leukemia, Cytogenetics and Molecular Genetics, Genomic complexity, Lymphoproliferative Disorders
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2020 17:39
Last modification date
23/11/2022 8:11
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