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

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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; Barbany, Gisela; Mansouri, Larry; Gunnarsson, Rebeqa; Parker, Helen; van den Berg, Eva; Bellido, Mar; Davis, Zadie; Wall, Meaghan; Scarpelli, Ilaria; Österborg, Anders; Hansson, Lotta; Jarosova, Marie; Ghia, Paolo; Poddighe, Pino; Espinet, Blanca; Pospisilova, Sarka; Tam, Constantine; Ysebaert, Loïc; Nguyen-Khac, Florence; Oscier, David; Haferlach, Claudia; Schoumans, Jacqueline; Stevens-Kroef, Marian; Eldering, Eric; Stamatopoulos, Kostas; Rosenquist, Richard; Strefford, Jonathan C.; Mellink, Clemens; Kater, Arnon P.

I: Haematologica, Vol. 105, Nr. 5, 2020.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Leeksma, AC, Baliakas, P, Moysiadis, T, Puiggros, A, Plevova, K, van der Kevie-Kersemaekers, AM, Posthuma, H, Rodriguez-Vicente, AE, Tran, AN, Barbany, G, Mansouri, L, Gunnarsson, R, Parker, H, van den Berg, E, Bellido, M, Davis, Z, Wall, M, Scarpelli, I, Österborg, A, Hansson, L, Jarosova, M, Ghia, P, Poddighe, P, Espinet, B, Pospisilova, S, Tam, C, Ysebaert, L, Nguyen-Khac, F, Oscier, D, Haferlach, C, Schoumans, J, Stevens-Kroef, M, Eldering, E, Stamatopoulos, K, Rosenquist, R, Strefford, JC, Mellink, C & Kater, AP 2020, 'Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: A multi-center study', Haematologica, vol. 105, nr. 5. https://doi.org/10.3324/HAEMATOL.2019.239947

APA

Leeksma, A. C., Baliakas, P., Moysiadis, T., Puiggros, A., Plevova, K., van der Kevie-Kersemaekers, A. M., ... Kater, A. P. (2020). Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: A multi-center study. Haematologica, 105(5). https://doi.org/10.3324/HAEMATOL.2019.239947

CBE

Leeksma AC, Baliakas P, Moysiadis T, Puiggros A, Plevova K, van der Kevie-Kersemaekers AM, Posthuma H, Rodriguez-Vicente AE, Tran AN, Barbany G, Mansouri L, Gunnarsson R, Parker H, van den Berg E, Bellido M, Davis Z, Wall M, Scarpelli I, Österborg A, Hansson L, Jarosova M, Ghia P, Poddighe P, Espinet B, Pospisilova S, Tam C, Ysebaert L, Nguyen-Khac F, Oscier D, Haferlach C, Schoumans J, Stevens-Kroef M, Eldering E, Stamatopoulos K, Rosenquist R, Strefford JC, Mellink C, Kater AP. 2020. Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: A multi-center study. Haematologica. 105(5). https://doi.org/10.3324/HAEMATOL.2019.239947

MLA

Vancouver

Leeksma AC, Baliakas P, Moysiadis T, Puiggros A, Plevova K, van der Kevie-Kersemaekers AM et al. Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: A multi-center study. Haematologica. 2020;105(5). https://doi.org/10.3324/HAEMATOL.2019.239947

Author

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 ; Barbany, Gisela ; Mansouri, Larry ; Gunnarsson, Rebeqa ; Parker, Helen ; van den Berg, Eva ; Bellido, Mar ; Davis, Zadie ; Wall, Meaghan ; Scarpelli, Ilaria ; Österborg, Anders ; Hansson, Lotta ; Jarosova, Marie ; Ghia, Paolo ; Poddighe, Pino ; Espinet, Blanca ; Pospisilova, Sarka ; Tam, Constantine ; Ysebaert, Loïc ; Nguyen-Khac, Florence ; Oscier, David ; Haferlach, Claudia ; Schoumans, Jacqueline ; Stevens-Kroef, Marian ; Eldering, Eric ; Stamatopoulos, Kostas ; Rosenquist, Richard ; Strefford, Jonathan C. ; Mellink, Clemens ; Kater, Arnon P. / Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity : A multi-center study. I: Haematologica. 2020 ; Vol. 105, Nr. 5.

RIS

TY - JOUR

T1 - Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity

T2 - A multi-center study

AU - Leeksma, Alexander C.

AU - Baliakas, Panagiotis

AU - Moysiadis, Theodoros

AU - Puiggros, Anna

AU - Plevova, Karla

AU - van der Kevie-Kersemaekers, Anne Marie

AU - Posthuma, Hidde

AU - Rodriguez-Vicente, Ana E.

AU - Tran, Anh Nhi

AU - Barbany, Gisela

AU - Mansouri, Larry

AU - Gunnarsson, Rebeqa

AU - Parker, Helen

AU - van den Berg, Eva

AU - Bellido, Mar

AU - Davis, Zadie

AU - Wall, Meaghan

AU - Scarpelli, Ilaria

AU - Österborg, Anders

AU - Hansson, Lotta

AU - Jarosova, Marie

AU - Ghia, Paolo

AU - Poddighe, Pino

AU - Espinet, Blanca

AU - Pospisilova, Sarka

AU - Tam, Constantine

AU - Ysebaert, Loïc

AU - Nguyen-Khac, Florence

AU - Oscier, David

AU - Haferlach, Claudia

AU - Schoumans, Jacqueline

AU - Stevens-Kroef, Marian

AU - Eldering, Eric

AU - Stamatopoulos, Kostas

AU - Rosenquist, Richard

AU - Strefford, Jonathan C.

AU - Mellink, Clemens

AU - Kater, Arnon P.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.3324/HAEMATOL.2019.239947

DO - 10.3324/HAEMATOL.2019.239947

M3 - Article

VL - 105

JO - Haematologica-The Hematology Journal

JF - Haematologica-The Hematology Journal

SN - 1592-8721

IS - 5

ER -