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  • Leeksma, Alexander C.Academic Medical Center of University of Amsterdam (AMC),University of Amsterdam (author)

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

  • Article/chapterEnglish2020

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  • 2020

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  • LIBRIS-ID:oai:lup.lub.lu.se:550e732e-dca8-4d3e-9ebf-88dc9d73d5c3
  • https://lup.lub.lu.se/record/550e732e-dca8-4d3e-9ebf-88dc9d73d5c3URI
  • https://doi.org/10.3324/HAEMATOL.2019.239947DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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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  • Baliakas, PanagiotisUppsala University (author)
  • Moysiadis, TheodorosCenter for Research and Technology Hellas (author)
  • Puiggros, AnnaHospital del Mar Medical Research Institute (author)
  • Plevova, KarlaMasaryk University,University Hospital Brno (author)
  • van der Kevie-Kersemaekers, Anne MarieAcademic Medical Center of University of Amsterdam (AMC),University of Amsterdam (author)
  • Posthuma, HiddeUniversity of Amsterdam,Academic Medical Center of University of Amsterdam (AMC) (author)
  • Rodriguez-Vicente, Ana E.University of Salamanca (author)
  • Tran, Anh NhiKarolinska Institute (author)
  • Barbany, GiselaKarolinska Institute (author)
  • Mansouri, LarryKarolinska Institute (author)
  • Gunnarsson, RebeqaLund University,Lunds universitet,Genetiska och epigenetiska studier av barnleukemi,Forskargrupper vid Lunds universitet,Genetic and epigenetic studies of pediatric leukemia,Lund University Research Groups(Swepub:lu)stem-rgu (author)
  • Parker, HelenUniversity of Southampton (author)
  • van den Berg, EvaUniversity Medical Center Groningen,University of Groningen (author)
  • Bellido, MarUniversity of Groningen,University Medical Center Groningen (author)
  • Davis, ZadieRoyal Bournemouth Hospital (author)
  • Wall, MeaghanSt. Vincent's Hospital, Melbourne (author)
  • Scarpelli, IlariaLausanne University Hospital (author)
  • Österborg, AndersKarolinska Institute (author)
  • Hansson, LottaKarolinska Institute (author)
  • Jarosova, MarieUniversity Hospital Brno,Masaryk University (author)
  • Ghia, PaoloSan Raffaele Hospital,Vita-Salute San Raffaele University (author)
  • Poddighe, PinoVrije Universiteit Amsterdam,Amsterdam UMC - Vrije Universiteit Amsterdam (author)
  • Espinet, BlancaHospital del Mar Medical Research Institute (author)
  • Pospisilova, SarkaMasaryk University,University Hospital Brno (author)
  • Tam, ConstantineUniversity of Melbourne,St. Vincent's Hospital, Melbourne (author)
  • Ysebaert, LoïcInstitut Universitaire du Cancer Toulouse (author)
  • Nguyen-Khac, FlorencePitié-Salpêtrière University Hospital (author)
  • Oscier, DavidRoyal Bournemouth Hospital (author)
  • Haferlach, ClaudiaMunich Leukemia Laboratory (MLL) (author)
  • Schoumans, JacquelineLausanne University Hospital (author)
  • Stevens-Kroef, MarianRadboud University Medical Center (author)
  • Eldering, EricAcademic Medical Center of University of Amsterdam (AMC),University of Amsterdam (author)
  • Stamatopoulos, KostasCenter for Research and Technology Hellas (author)
  • Rosenquist, RichardKarolinska Institute (author)
  • Strefford, Jonathan C.University of Southampton (author)
  • Mellink, ClemensAcademic Medical Center of University of Amsterdam (AMC),University of Amsterdam (author)
  • Kater, Arnon P.Academic Medical Center of University of Amsterdam (AMC),University of Amsterdam (author)
  • Academic Medical Center of University of Amsterdam (AMC)University of Amsterdam (creator_code:org_t)

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  • In:Haematologica105:50390-6078

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