Cytogenetic complexity in chronic lymphocytic leukemia:
definitions, associations, and clinical impact

J 2019

Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact

BALIAKAS, P., S. JEROMIN, M. ISKAS, A. PUIGGROS, Karla PLEVOVÁ et. al.

Basic information

Original name

Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact

Authors

BALIAKAS, P. (752 Sweden), S. JEROMIN (276 Germany), M. ISKAS (300 Greece), A. PUIGGROS (724 Spain), Karla PLEVOVÁ (203 Czech Republic, belonging to the institution), F. NGUYEN-KHAC (250 France), Z. DAVIS (826 United Kingdom of Great Britain and Northern Ireland), G.M. RIGOLIN (380 Italy), A. VISENTIN (380 Italy), A. XOCHELLI (300 Greece), J. DELGADO (724 Spain), F. BARAN-MARSZAK (250 France), E. STALIKA (300 Greece), P. ABRISQUETA (724 Spain), Kristina ĎURECHOVÁ (203 Czech Republic, belonging to the institution), G. PAPAIOANNOU (300 Greece), V. ECLACHE (250 France), M. DIMOU (300 Greece), T. ILIAKIS (300 Greece), R. COLLADO (724 Spain), Michael DOUBEK (203 Czech Republic, belonging to the institution), M.J. CALASANZ (724 Spain), N. RUIZ-XIVILLE (724 Spain), C. MORENO (724 Spain), Marie JAROŠOVÁ (203 Czech Republic, belonging to the institution), A.C. LEEKSMA (528 Netherlands), P. PANAYIOTIDIS (300 Greece), H. PODGORNIK (705 Slovenia), F. CYMBALISTA (250 France), A. ANAGNOSTOPOULOS (300 Greece), L. TRENTIN (380 Italy), N. STAVROYIANNI (300 Greece), F. DAVI (250 France), P. GHIA (380 Italy), A.P. KATER (528 Netherlands), A. CUNEO (380 Italy), Šárka POSPÍŠILOVÁ (203 Czech Republic, guarantor, belonging to the institution), B. ESPINET (724 Spain), A. ATHANASIADOU (300 Greece), D. OSCIER (826 United Kingdom of Great Britain and Northern Ireland), C. HAFERLACH (276 Germany) and K. STAMATOPOULOS (300 Greece)

Edition

Blood, Washington DC, USA, American Society of Hematology, 2019, 0006-4971

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 17.794

RIV identification code

RIV/00216224:14740/19:00108484

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1182/blood-2018-09-873083

UT WoS

000461508300007

Keywords in English

HEALTH-ORGANIZATION CLASSIFICATION; CHROMOSOME-BANDING ANALYSIS; RISK GENOMIC ABERRATIONS; IN-SITU HYBRIDIZATION; CLL PATIENTS; CONVENTIONAL CYTOGENETICS; CLONAL EVOLUTION; RECURRENT MUTATIONS; CPG OLIGONUCLEOTIDE; PROGNOSTIC INDEX

Abstract

V originále

Recent evidence suggests that complex karyotype (CK) defined by the presence of >= 3 chromosomal aberrations (structural and/or numerical) identified by using chromosome-banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges toward the routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with >= 5 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcomes, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and/or TP53 mutations [TP53abs]), and the expression of somatically hypermutated (M-CLL) or unmutated immunoglobulin heavy variable genes. Thus, they contrasted with CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53abs. At the other end of the spectrum, patients with CK and 112,119 displayed an exceptionally indolent profile. Building upon CK, TP53abs, and immunoglobulin heavy variable gene somatic hyper-mutation status, we propose a novel hierarchical model in which patients with high-CK exhibit the worst prognosis, whereas those with mutated CLL lacking CK or TP53abs, as well as CK with 112,119, show the longest overall survival. Thus, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with >= 5 chromosomal aberrations emerges as prognostically adverse, independent of other biomarkers. Prospective clinical validation is warranted before ultimately incorporating high-CK in risk stratification of CLL.

Links

NV15-30015A, research and development project

Name: Analýza klonální heterogenity chronické lymfocytární leukemie pomoci sekvenování nové generace genu pro B-buněčný receptor. Národní studie.

NV15-31834A, research and development project

Name: Vliv selekce genomických poškození na průběh chronické lymfocytární leukémie

Citovat

BALIAKAS, P., S. JEROMIN, M. ISKAS, A. PUIGGROS, Karla PLEVOVÁ, F. NGUYEN-KHAC, Z. DAVIS, G.M. RIGOLIN, A. VISENTIN, A. XOCHELLI, J. DELGADO, F. BARAN-MARSZAK, E. STALIKA, P. ABRISQUETA, Kristina ĎURECHOVÁ, G. PAPAIOANNOU, V. ECLACHE, M. DIMOU, T. ILIAKIS, R. COLLADO, Michael DOUBEK, M.J. CALASANZ, N. RUIZ-XIVILLE, C. MORENO, Marie JAROŠOVÁ, A.C. LEEKSMA, P. PANAYIOTIDIS, H. PODGORNIK, F. CYMBALISTA, A. ANAGNOSTOPOULOS, L. TRENTIN, N. STAVROYIANNI, F. DAVI, P. GHIA, A.P. KATER, A. CUNEO, Šárka POSPÍŠILOVÁ, B. ESPINET, A. ATHANASIADOU, D. OSCIER, C. HAFERLACH and K. STAMATOPOULOS. Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact. Blood. Washington DC, USA: American Society of Hematology, 2019, vol. 133, No 11, p. 1205-1216. ISSN 0006-4971. Available from: https://dx.doi.org/10.1182/blood-2018-09-873083.

@article{1539523,
   author = {Baliakas, P. and Jeromin, S. and Iskas, M. and Puiggros, A. and Plevová, Karla and NguyenandKhac, F. and Davis, Z. and Rigolin, G.M. and Visentin, A. and Xochelli, A. and Delgado, J. and BaranandMarszak, F. and Stalika, E. and Abrisqueta, P. and Ďurechová, Kristina and Papaioannou, G. and Eclache, V. and Dimou, M. and Iliakis, T. and Collado, R. and Doubek, Michael and Calasanz, M.J. and RuizandXiville, N. and Moreno, C. and Jarošová, Marie and Leeksma, A.C. and Panayiotidis, P. and Podgornik, H. and Cymbalista, F. and Anagnostopoulos, A. and Trentin, L. and Stavroyianni, N. and Davi, F. and Ghia, P. and Kater, A.P. and Cuneo, A. and Pospíšilová, Šárka and Espinet, B. and Athanasiadou, A. and Oscier, D. and Haferlach, C. and Stamatopoulos, K.},
   article_location = {Washington DC, USA},
   article_number = {11},
   doi = {http://dx.doi.org/10.1182/blood-2018-09-873083},
   keywords = {HEALTH-ORGANIZATION CLASSIFICATION; CHROMOSOME-BANDING ANALYSIS; RISK GENOMIC ABERRATIONS; IN-SITU HYBRIDIZATION; CLL PATIENTS; CONVENTIONAL CYTOGENETICS; CLONAL EVOLUTION; RECURRENT MUTATIONS; CPG OLIGONUCLEOTIDE; PROGNOSTIC INDEX},
   language = {eng},
   issn = {0006-4971},
   journal = {Blood},
   title = {Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact},
   url = {http://www.bloodjournal.org/content/133/11/1205?sso-checked=true},
   volume = {133},
   year = {2019}
}

TY  - JOUR
ID  - 1539523
AU  - Baliakas, P. - Jeromin, S. - Iskas, M. - Puiggros, A. - Plevová, Karla - Nguyen-Khac, F. - Davis, Z. - Rigolin, G.M. - Visentin, A. - Xochelli, A. - Delgado, J. - Baran-Marszak, F. - Stalika, E. - Abrisqueta, P. - Ďurechová, Kristina - Papaioannou, G. - Eclache, V. - Dimou, M. - Iliakis, T. - Collado, R. - Doubek, Michael - Calasanz, M.J. - Ruiz-Xiville, N. - Moreno, C. - Jarošová, Marie - Leeksma, A.C. - Panayiotidis, P. - Podgornik, H. - Cymbalista, F. - Anagnostopoulos, A. - Trentin, L. - Stavroyianni, N. - Davi, F. - Ghia, P. - Kater, A.P. - Cuneo, A. - Pospíšilová, Šárka - Espinet, B. - Athanasiadou, A. - Oscier, D. - Haferlach, C. - Stamatopoulos, K.
PY  - 2019
TI  - Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact
JF  - Blood
VL  - 133
IS  - 11
SP  - 1205-1216
EP  - 1205-1216
PB  - American Society of Hematology
SN  - 00064971
KW  - HEALTH-ORGANIZATION CLASSIFICATION
KW  - CHROMOSOME-BANDING ANALYSIS
KW  - RISK GENOMIC ABERRATIONS
KW  - IN-SITU HYBRIDIZATION
KW  - CLL PATIENTS
KW  - CONVENTIONAL CYTOGENETICS
KW  - CLONAL EVOLUTION
KW  - RECURRENT MUTATIONS
KW  - CPG OLIGONUCLEOTIDE
KW  - PROGNOSTIC INDEX
UR  - http://www.bloodjournal.org/content/133/11/1205?sso-checked=true
L2  - http://www.bloodjournal.org/content/133/11/1205?sso-checked=true
N2  - Recent evidence suggests that complex karyotype (CK) defined by the presence of >= 3 chromosomal aberrations (structural and/or numerical) identified by using chromosome-banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges toward the routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with >= 5 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcomes, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and/or TP53 mutations [TP53abs]), and the expression of somatically hypermutated (M-CLL) or unmutated immunoglobulin heavy variable genes. Thus, they contrasted with CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53abs. At the other end of the spectrum, patients with CK and 112,119 displayed an exceptionally indolent profile. Building upon CK, TP53abs, and immunoglobulin heavy variable gene somatic hyper-mutation status, we propose a novel hierarchical model in which patients with high-CK exhibit the worst prognosis, whereas those with mutated CLL lacking CK or TP53abs, as well as CK with 112,119, show the longest overall survival. Thus, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with >= 5 chromosomal aberrations emerges as prognostically adverse, independent of other biomarkers. Prospective clinical validation is warranted before ultimately incorporating high-CK in risk stratification of CLL.
ER  -

BALIAKAS, P., S. JEROMIN, M. ISKAS, A. PUIGGROS, Karla PLEVOVÁ, F. NGUYEN-KHAC, Z. DAVIS, G.M. RIGOLIN, A. VISENTIN, A. XOCHELLI, J. DELGADO, F. BARAN-MARSZAK, E. STALIKA, P. ABRISQUETA, Kristina ĎURECHOVÁ, G. PAPAIOANNOU, V. ECLACHE, M. DIMOU, T. ILIAKIS, R. COLLADO, Michael DOUBEK, M.J. CALASANZ, N. RUIZ-XIVILLE, C. MORENO, Marie JAROŠOVÁ, A.C. LEEKSMA, P. PANAYIOTIDIS, H. PODGORNIK, F. CYMBALISTA, A. ANAGNOSTOPOULOS, L. TRENTIN, N. STAVROYIANNI, F. DAVI, P. GHIA, A.P. KATER, A. CUNEO, Šárka POSPÍŠILOVÁ, B. ESPINET, A. ATHANASIADOU, D. OSCIER, C. HAFERLACH and K. STAMATOPOULOS. Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact. \textit{Blood}. Washington DC, USA: American Society of Hematology, 2019, vol.~133, No~11, p.~1205-1216. ISSN~0006-4971. Available from: https://dx.doi.org/10.1182/blood-2018-09-873083.

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