Genomic arrays identify high-risk chronic lymphocytic leukemia
with genomic complexity: a multicenter study

J 2021

Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multicenter study

LEEKSMA, A. C., P. BALIAKAS, T. MOYSIADIS, A. PUIGGROS, Karla PLEVOVÁ et. al.

Basic information

Original name

Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multicenter study

Authors

LEEKSMA, A. C., P. BALIAKAS, T. MOYSIADIS, A. PUIGGROS, Karla PLEVOVÁ (203 Czech Republic, belonging to the institution), A. M. VAND ER KEVIE-KERSEMAEKERS, H. POSTHUMA, A. E. RODRIGUEZ-VICENTE, A. N. TRAN, G. BARBANY, L. MANSOURI, R. GUNNARSSON, H. PARKER, E. VAN DEN BERG, M. BELLIDO, Z. DAVIS, M. WALL, I. SCARPELLI, A. OSTERBORG, L. HANSSON, Marie JAROŠOVÁ (203 Czech Republic, belonging to the institution), P. GHIA, P. PODDIGHE, B. ESPINET, Šárka POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution), C. TAM, L. YSEBAERT, F. NGUYEN-KHAC, D. OSCIER, C. HAFERLACH, J. SCHOUMANS, M. STEVENS-KROEF, E. ELDERING, K. STAMATOPOULOS, R. ROSENQUIST, J. C. STREFFORD, C. MELLINK and A. P. KATER (guarantor)

Edition

Haematologica, PAVIA, FERRATA STORTI FOUNDATION, 2021, 0390-6078

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

Italy

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 11.047

RIV identification code

RIV/00216224:14110/21:00121109

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3324/haematol.2019.239947

UT WoS

000606523300003

Keywords in English

Genomic arrays; chronic lymphocytic leukemia

Abstract

V originále

Complex karyotype identified by chromosome-banding analysis has been shown to have prognostic value in chronic lymphocytic leukemia (CLL). Genomic arrays offer high-resolution genomewide detection of copy-number alterations (CNA) and could therefore be well equipped to detect the presence of a complex karyotype. Current knowledge on genomic arrays in CLL is based on outcomes of single-cen ter 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 2,293 arrays from 13 diagnostic laboratories according to established standards. CNA were found outside regions captured by CLL fluorescence in situ hybridization 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 into three distinct prognostic subgroups based on the number of CNA. In multivariable analysis only high genomic complexity, defined as z5 CNA, emerged as an independent adverse prognosticator for time to first treatment (hazard ratio: 2.15; 95% confidence interval: 1.36-3.41; P=0.001) and overall survival (hazard ratio: 2.54, 95% confidence interval: 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, in terms of risk stratification, performed at least as well as simultaneous chromosome banding analysis as carried out in 122 patients. Our findings indicate that genomic array is an accurate tool for CLL risk stratification.

Links

LM2015064, research and development project

Name: Český národní uzel Evropské infrastruktury pro translační medicínu (Acronym: EATRIS-ERIC-CZ)

Investor: Ministry of Education, Youth and Sports of the CR

LM2015091, research and development project

Name: Národní centrum lékařské genomiky (Acronym: NCLG)

Investor: Ministry of Education, Youth and Sports of the CR

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

LEEKSMA, A. C., P. BALIAKAS, T. MOYSIADIS, A. PUIGGROS, Karla PLEVOVÁ, A. M. VAND ER KEVIE-KERSEMAEKERS, H. POSTHUMA, A. E. RODRIGUEZ-VICENTE, A. N. TRAN, G. BARBANY, L. MANSOURI, R. GUNNARSSON, H. PARKER, E. VAN DEN BERG, M. BELLIDO, Z. DAVIS, M. WALL, I. SCARPELLI, A. OSTERBORG, L. HANSSON, Marie JAROŠOVÁ, P. GHIA, P. PODDIGHE, B. ESPINET, Šárka POSPÍŠILOVÁ, C. TAM, L. YSEBAERT, F. NGUYEN-KHAC, D. OSCIER, C. HAFERLACH, J. SCHOUMANS, M. STEVENS-KROEF, E. ELDERING, K. STAMATOPOULOS, R. ROSENQUIST, J. C. STREFFORD, C. MELLINK and A. P. KATER. Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multicenter study. Haematologica. PAVIA: FERRATA STORTI FOUNDATION, 2021, vol. 106, No 1, p. 87-97. ISSN 0390-6078. Available from: https://dx.doi.org/10.3324/haematol.2019.239947.

@article{1739856,
   author = {Leeksma, A. C. and Baliakas, P. and Moysiadis, T. and Puiggros, A. and Plevová, Karla and vand er KevieandKersemaekers, A. M. and Posthuma, H. and RodriguezandVicente, A. E. and Tran, A. N. and Barbany, G. and Mansouri, L. and Gunnarsson, R. and Parker, H. and van den Berg, E. and Bellido, M. and Davis, Z. and Wall, M. and Scarpelli, I. and Osterborg, A. and Hansson, L. and Jarošová, Marie and Ghia, P. and Poddighe, P. and Espinet, B. and Pospíšilová, Šárka and Tam, C. and Ysebaert, L. and NguyenandKhac, F. and Oscier, D. and Haferlach, C. and Schoumans, J. and StevensandKroef, M. and Eldering, E. and Stamatopoulos, K. and Rosenquist, R. and Strefford, J. C. and Mellink, C. and Kater, A. P.},
   article_location = {PAVIA},
   article_number = {1},
   doi = {http://dx.doi.org/10.3324/haematol.2019.239947},
   keywords = {Genomic arrays; chronic lymphocytic leukemia},
   language = {eng},
   issn = {0390-6078},
   journal = {Haematologica},
   title = {Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multicenter study},
   url = {https://haematologica.org/article/view/9623},
   volume = {106},
   year = {2021}
}

TY  - JOUR
ID  - 1739856
AU  - Leeksma, A. C. - Baliakas, P. - Moysiadis, T. - Puiggros, A. - Plevová, Karla - vand er Kevie-Kersemaekers, A. M. - Posthuma, H. - Rodriguez-Vicente, A. E. - Tran, A. N. - Barbany, G. - Mansouri, L. - Gunnarsson, R. - Parker, H. - van den Berg, E. - Bellido, M. - Davis, Z. - Wall, M. - Scarpelli, I. - Osterborg, A. - Hansson, L. - Jarošová, Marie - Ghia, P. - Poddighe, P. - Espinet, B. - Pospíšilová, Šárka - Tam, C. - Ysebaert, L. - Nguyen-Khac, F. - Oscier, D. - Haferlach, C. - Schoumans, J. - Stevens-Kroef, M. - Eldering, E. - Stamatopoulos, K. - Rosenquist, R. - Strefford, J. C. - Mellink, C. - Kater, A. P.
PY  - 2021
TI  - Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multicenter study
JF  - Haematologica
VL  - 106
IS  - 1
SP  - 87-97
EP  - 87-97
PB  - FERRATA STORTI FOUNDATION
SN  - 03906078
KW  - Genomic arrays
KW  - chronic lymphocytic leukemia
UR  - https://haematologica.org/article/view/9623
L2  - https://haematologica.org/article/view/9623
N2  - Complex karyotype identified by chromosome-banding analysis has been shown to have prognostic value in chronic lymphocytic leukemia (CLL). Genomic arrays offer high-resolution genomewide detection of copy-number alterations (CNA) and could therefore be well equipped to detect the presence of a complex karyotype. Current knowledge on genomic arrays in CLL is based on outcomes of single-cen ter 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 2,293 arrays from 13 diagnostic laboratories according to established standards. CNA were found outside regions captured by CLL fluorescence in situ hybridization 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 into three distinct prognostic subgroups based on the number of CNA. In multivariable analysis only high genomic complexity, defined as z5 CNA, emerged as an independent adverse prognosticator for time to first treatment (hazard ratio: 2.15; 95% confidence interval: 1.36-3.41; P=0.001) and overall survival (hazard ratio: 2.54, 95% confidence interval: 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, in terms of risk stratification, performed at least as well as simultaneous chromosome banding analysis as carried out in 122 patients. Our findings indicate that genomic array is an accurate tool for CLL risk stratification.
ER  -

LEEKSMA, A. C., P. BALIAKAS, T. MOYSIADIS, A. PUIGGROS, Karla PLEVOVÁ, A. M. VAND ER KEVIE-KERSEMAEKERS, H. POSTHUMA, A. E. RODRIGUEZ-VICENTE, A. N. TRAN, G. BARBANY, L. MANSOURI, R. GUNNARSSON, H. PARKER, E. VAN DEN BERG, M. BELLIDO, Z. DAVIS, M. WALL, I. SCARPELLI, A. OSTERBORG, L. HANSSON, Marie JAROŠOVÁ, P. GHIA, P. PODDIGHE, B. ESPINET, Šárka POSPÍŠILOVÁ, C. TAM, L. YSEBAERT, F. NGUYEN-KHAC, D. OSCIER, C. HAFERLACH, J. SCHOUMANS, M. STEVENS-KROEF, E. ELDERING, K. STAMATOPOULOS, R. ROSENQUIST, J. C. STREFFORD, C. MELLINK and A. P. KATER. Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multicenter study. \textit{Haematologica}. PAVIA: FERRATA STORTI FOUNDATION, 2021, vol.~106, No~1, p.~87-97. ISSN~0390-6078. Available from: https://dx.doi.org/10.3324/haematol.2019.239947.

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