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

on behalf of ERIC, the European Research Initiative on CLL

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Recent evidence suggests that complex karyotype (CK) defined by the presence of ≥3 chromosomal aberrations (structural and/or numerical) identified by using chromosomebanding 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 +12,+19 displayed an exceptionally indolent profile. Building upon CK, TP53abs, and immunoglobulin heavy variable gene somatic hypermutation 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 +12,+19, 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.
Original languageEnglish
Pages (from-to)1205-1216
JournalBlood
Volume133
Issue number11
DOIs
Publication statusPublished - 2019

Cite this

on behalf of ERIC, the European Research Initiative on CLL. / Cytogenetic complexity in chronic lymphocytic leukemia: Definitions, associations, and clinical impact. In: Blood. 2019 ; Vol. 133, No. 11. pp. 1205-1216.
@article{b867c57aafe54e19b8df703e51988b12,
title = "Cytogenetic complexity in chronic lymphocytic leukemia: Definitions, associations, and clinical impact",
abstract = "Recent evidence suggests that complex karyotype (CK) defined by the presence of ≥3 chromosomal aberrations (structural and/or numerical) identified by using chromosomebanding 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 +12,+19 displayed an exceptionally indolent profile. Building upon CK, TP53abs, and immunoglobulin heavy variable gene somatic hypermutation 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 +12,+19, 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.",
author = "{on behalf of ERIC, the European Research Initiative on CLL} and Panagiotis Baliakas and Sabine Jeromin and Michalis Iskas and Anna Puiggros and Karla Plevova and Florence Nguyen-Khac and Zadie Davis and {Matteo Rigolin}, Gian and Andrea Visentin and Aliki Xochelli and Julio Delgado and Fanny Baran-Marszak and Evangelia Stalika and Pau Abrisqueta and Kristina Durechova and George Papaioannou and Virginie Eclache and Maria DImou and Theodoros Iliakis and Rosa Collado and Michael Doubek and Calasanz, {M. Jose} and Neus Ruiz-Xiville and Carolina Moreno and Marie Jarosova and Leeksma, {Alexander C.} and Panayiotis Panayiotidis and Helena Podgornik and Florence Cymbalista and Achilles Anagnostopoulos and Livio Trentin and Niki Stavroyianni and Fred Davi and Paolo Ghia and Kater, {Arnon P.} and Antonio Cuneo and Sarka Pospisilova and Blanca Espinet and Anastasia Athanasiadou and David Oscier and Claudia Haferlach and Kostas Stamatopoulos",
year = "2019",
doi = "10.1182/blood-2018-09-873083",
language = "English",
volume = "133",
pages = "1205--1216",
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on behalf of ERIC, the European Research Initiative on CLL 2019, 'Cytogenetic complexity in chronic lymphocytic leukemia: Definitions, associations, and clinical impact' Blood, vol. 133, no. 11, pp. 1205-1216. https://doi.org/10.1182/blood-2018-09-873083

Cytogenetic complexity in chronic lymphocytic leukemia: Definitions, associations, and clinical impact. / on behalf of ERIC, the European Research Initiative on CLL.

In: Blood, Vol. 133, No. 11, 2019, p. 1205-1216.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Cytogenetic complexity in chronic lymphocytic leukemia: Definitions, associations, and clinical impact

AU - on behalf of ERIC, the European Research Initiative on CLL

AU - Baliakas, Panagiotis

AU - Jeromin, Sabine

AU - Iskas, Michalis

AU - Puiggros, Anna

AU - Plevova, Karla

AU - Nguyen-Khac, Florence

AU - Davis, Zadie

AU - Matteo Rigolin, Gian

AU - Visentin, Andrea

AU - Xochelli, Aliki

AU - Delgado, Julio

AU - Baran-Marszak, Fanny

AU - Stalika, Evangelia

AU - Abrisqueta, Pau

AU - Durechova, Kristina

AU - Papaioannou, George

AU - Eclache, Virginie

AU - DImou, Maria

AU - Iliakis, Theodoros

AU - Collado, Rosa

AU - Doubek, Michael

AU - Calasanz, M. Jose

AU - Ruiz-Xiville, Neus

AU - Moreno, Carolina

AU - Jarosova, Marie

AU - Leeksma, Alexander C.

AU - Panayiotidis, Panayiotis

AU - Podgornik, Helena

AU - Cymbalista, Florence

AU - Anagnostopoulos, Achilles

AU - Trentin, Livio

AU - Stavroyianni, Niki

AU - Davi, Fred

AU - Ghia, Paolo

AU - Kater, Arnon P.

AU - Cuneo, Antonio

AU - Pospisilova, Sarka

AU - Espinet, Blanca

AU - Athanasiadou, Anastasia

AU - Oscier, David

AU - Haferlach, Claudia

AU - Stamatopoulos, Kostas

PY - 2019

Y1 - 2019

N2 - Recent evidence suggests that complex karyotype (CK) defined by the presence of ≥3 chromosomal aberrations (structural and/or numerical) identified by using chromosomebanding 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 +12,+19 displayed an exceptionally indolent profile. Building upon CK, TP53abs, and immunoglobulin heavy variable gene somatic hypermutation 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 +12,+19, 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.

AB - Recent evidence suggests that complex karyotype (CK) defined by the presence of ≥3 chromosomal aberrations (structural and/or numerical) identified by using chromosomebanding 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 +12,+19 displayed an exceptionally indolent profile. Building upon CK, TP53abs, and immunoglobulin heavy variable gene somatic hypermutation 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 +12,+19, 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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85062952890&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30602617

U2 - 10.1182/blood-2018-09-873083

DO - 10.1182/blood-2018-09-873083

M3 - Article

VL - 133

SP - 1205

EP - 1216

JO - Blood

JF - Blood

SN - 0006-4971

IS - 11

ER -