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

Leeksma, Alexander C. ; Baliakas, Panagiotis ; Moysiadis, Theodoros ; Puiggros, Anna ; Plevova, Karla ; van der Kevie-Kersemaekers, Anne Marie ; Posthuma, Hidde ; Rodriguez-Vicente, Ana E. ; Tran, Anh Nhi and Barbany, Gisela , et al. (2020) In Haematologica 105(5).
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... (More)

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.

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type
Contribution to journal
publication status
published
subject
in
Haematologica
volume
105
issue
5
publisher
Ferrata Storti Foundation
external identifiers
  • scopus:85085211294
  • pmid:31974198
ISSN
0390-6078
DOI
10.3324/HAEMATOL.2019.239947
language
English
LU publication?
yes
id
550e732e-dca8-4d3e-9ebf-88dc9d73d5c3
date added to LUP
2020-06-23 11:05:33
date last changed
2021-02-17 01:16:13
@article{550e732e-dca8-4d3e-9ebf-88dc9d73d5c3,
  abstract     = {<p>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&lt;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&lt;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.</p>},
  author       = {Leeksma, Alexander C. and Baliakas, Panagiotis and Moysiadis, Theodoros and Puiggros, Anna and Plevova, Karla and van der Kevie-Kersemaekers, Anne Marie and Posthuma, Hidde and Rodriguez-Vicente, Ana E. and Tran, Anh Nhi and Barbany, Gisela and Mansouri, Larry and Gunnarsson, Rebeqa and Parker, Helen and van den Berg, Eva and Bellido, Mar and Davis, Zadie and Wall, Meaghan and Scarpelli, Ilaria and Österborg, Anders and Hansson, Lotta and Jarosova, Marie and Ghia, Paolo and Poddighe, Pino and Espinet, Blanca and Pospisilova, Sarka and Tam, Constantine and Ysebaert, Loïc and Nguyen-Khac, Florence and Oscier, David and Haferlach, Claudia and Schoumans, Jacqueline and Stevens-Kroef, Marian and Eldering, Eric and Stamatopoulos, Kostas and Rosenquist, Richard and Strefford, Jonathan C. and Mellink, Clemens and Kater, Arnon P.},
  issn         = {0390-6078},
  language     = {eng},
  number       = {5},
  publisher    = {Ferrata Storti Foundation},
  series       = {Haematologica},
  title        = {Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity : A multi-center study},
  url          = {http://dx.doi.org/10.3324/HAEMATOL.2019.239947},
  doi          = {10.3324/HAEMATOL.2019.239947},
  volume       = {105},
  year         = {2020},
}