Haematologica (Jan 2020)
Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multi-center study
- 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,
- Rebeqa Gunnarsson,
- 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
Affiliations
- Alexander C. Leeksma
- Amsterdam University Medical Centers, University of Amsterdam
- Panagiotis Baliakas
- Dept of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden;
- Theodoros Moysiadis
- Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece;
- Anna Puiggros
- Hospital del Mar, Barcelona;
- Karla Plevova
- University Hospital Brno, Masaryk University, Brno, Czech Republic
- Anne-Marie van der Kevie-Kersemaekers
- Dept of Clinical Genetics, Amsterdam University Medical Centers, Univ of Amsterdam, The Netherlands;
- Hidde Posthuma
- Dept of Clinical Genetics, Amsterdam University Medical Centers, Univ of Amsterdam, The Netherlands;
- Ana E. Rodriguez-Vicente
- IBSAL, IBMCC, Centro de Investigación del Cancer, Universidad de Salamanca-CSIC, Spain;
- Anh Nhi Tran
- Dept of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden;
- Gisela Barbany
- Dept of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden;
- Larry Mansouri
- Dept of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden;
- Rebeqa Gunnarsson
- Division of Clinical Genetics, Dept of Laboratory Medicine, Lund University, Lund, Sweden;
- Helen Parker
- Cancer Genomics, Academic Unit of Cancer Sciences, University of Southampton, Southampton, UK;
- Eva van den Berg
- Dept of Genetics, University Medical Center Groningen, University of Groningen, The Netherlands;
- Mar Bellido
- Dept of Genetics, University Medical Center Groningen, University of Groningen, The Netherlands;
- Zadie Davis
- Dept of Molecular Pathology, Royal Bournemouth Hospital, Bournemouth, UK;
- Meaghan Wall
- Cytogenetics department, St Vincent Hospital Melbourne, Victoria, Australia;
- Ilaria Scarpelli
- Oncogenomic laboratory, Dept of Hematology, Lausanne University Hospital (CHUV), Switzerland;
- Anders Österborg
- Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden;
- Lotta Hansson
- Department of Oncology-Pathology, Karolinska Institutet, Stockholm;
- Marie Jarosova
- University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic;
- Paolo Ghia
- Dept. of Experimental Oncology, IRCCS Ospedale San Raffaele, Università Vita-Salute, Milan;
- Pino Poddighe
- Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, The Netherlands;
- Blanca Espinet
- Laboratori de Citogenetica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain;
- Sarka Pospisilova
- CEITEC, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic;
- Constantine Tam
- St Vincent Hospital Melbourne, Peter MacCallum Cancer Center, University of Melbourne, Australia;
- Loïc Ysebaert
- Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France;
- Florence Nguyen-Khac
- Service d'Hematologie Biologique, Hopital Pitié-Salpetriere, APHP, Paris, France;
- David Oscier
- Dept of Molecular Pathology, Royal Bournemouth Hospital, Bournemouth, UK;
- Claudia Haferlach
- MLL Munich Leukemia Laboratory, Munich, Germany;
- Jacqueline Schoumans
- Oncogenomic laboratory, Dept of Hematology, Lausanne University Hospital (CHUV), Switzerland;
- Marian Stevens-Kroef
- Radboud University Medical Center, Dept of Human Genetics, Nijmegen, The Netherlands;
- Eric Eldering
- Amsterdam University Medical Centers, University of Amsterdam, The Netherlands;
- Kostas Stamatopoulos
- Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece;
- Richard Rosenquist
- Dept of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden;
- Jonathan C. Strefford
- Cancer Genomics, Academic Unit of Cancer Sciences, University of Southampton
- Clemens Mellink
- Amsterdam University Medical Centers, University of Amsterdam, The Netherlands;
- Arnon P. Kater
- Hematology, Amsterdam University Medical Centers, University of Amsterdam, The Netherlands
- DOI
- https://doi.org/10.3324/haematol.2019.239947
- Journal volume & issue
-
Vol. 106,
no. 1
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.
