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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Alexander C. Leeksma
  • Panagiotis Baliakas
  • Theodoros Moysiadis
  • Anna Puiggros
  • Karla Plevova
  • Anne Marie van der Kevie-Kersemaekers
  • Hidde Posthuma
  • Ana E. Rodriguez-Vicente
  • Anh Nhi Tran
  • Gisela Barbany
  • Larry Mansouri
  • Helen Parker
  • Eva van den Berg
  • Mar Bellido
  • Zadie Davis
  • Meaghan Wall
  • Ilaria Scarpelli
  • Anders Österborg
  • Lotta Hansson
  • Marie Jarosova
  • Paolo Ghia
  • Pino Poddighe
  • Blanca Espinet
  • Sarka Pospisilova
  • Constantine Tam
  • Loïc Ysebaert
  • Florence Nguyen-Khac
  • David Oscier
  • Claudia Haferlach
  • Jacqueline Schoumans
  • Marian Stevens-Kroef
  • Eric Eldering
  • Kostas Stamatopoulos
  • Richard Rosenquist
  • Jonathan C. Strefford
  • Clemens Mellink
  • Arnon P. Kater
Organisations
External organisations
  • Uppsala University
  • Center for Research and Technology Hellas
  • Hospital del Mar Medical Research Institute
  • University Hospital Brno
  • Masaryk University
  • University of Salamanca
  • University of Southampton
  • University Medical Center Groningen
  • Royal Bournemouth Hospital
  • St. Vincent's Hospital, Melbourne
  • Lausanne University Hospital
  • Vita-Salute San Raffaele University
  • University of Melbourne
  • Munich Leukemia Laboratory (MLL)
  • Radboud University Medical Center
  • University of Amsterdam
  • University of Groningen
  • San Raffaele Hospital
  • Vrije Universiteit Amsterdam
  • Amsterdam UMC - Vrije Universiteit Amsterdam
  • Institut Universitaire du Cancer Toulouse
  • Pitié-Salpêtrière University Hospital
  • Academic Medical Center of University of Amsterdam (AMC)
  • Karolinska Institutet
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology
  • Medical Genetics
Original languageEnglish
JournalHaematologica
Volume105
Issue number5
Publication statusPublished - 2020
Publication categoryResearch
Peer-reviewedYes