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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Bibtex

@article{550e732edca84d3e9ebf88dc9d73d5c3,
title = "Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: A multi-center study",
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.",
author = "Leeksma, {Alexander C.} and Panagiotis Baliakas and Theodoros Moysiadis and Anna Puiggros and Karla Plevova and {van der Kevie-Kersemaekers}, {Anne Marie} and Hidde Posthuma and Rodriguez-Vicente, {Ana E.} and Tran, {Anh Nhi} and Gisela Barbany and Larry Mansouri and Rebeqa Gunnarsson and Helen Parker and {van den Berg}, Eva and Mar Bellido and Zadie Davis and Meaghan Wall and Ilaria Scarpelli and Anders {\"O}sterborg and Lotta Hansson and Marie Jarosova and Paolo Ghia and Pino Poddighe and Blanca Espinet and Sarka Pospisilova and Constantine Tam and Lo{\"i}c Ysebaert and Florence Nguyen-Khac and David Oscier and Claudia Haferlach and Jacqueline Schoumans and Marian Stevens-Kroef and Eric Eldering and Kostas Stamatopoulos and Richard Rosenquist and Strefford, {Jonathan C.} and Clemens Mellink and Kater, {Arnon P.}",
year = "2020",
doi = "10.3324/HAEMATOL.2019.239947",
language = "English",
volume = "105",
journal = "Haematologica-The Hematology Journal",
issn = "1592-8721",
publisher = "Ferrata Storti Foundation",
number = "5",

}