Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact
Panagiotis Baliakas
(1)
,
Sabine Jeromin
(2)
,
Michalis Iskas
(3)
,
Anna Puiggros
(4)
,
Karla Plevova
(5, 6, 7)
,
Florence Nguyen-Khac
(8)
,
Zadie Davis
(9)
,
Gian Matteo Rigolin
(10)
,
Andrea Visentin
(11)
,
Aliki Xochelli
(12)
,
Julio Delgado
(13)
,
Fanny Baran-Marszak
(14, 15)
,
Evangelia Stalika
(12)
,
Pau Abrisqueta
(16)
,
Kristina Durechova
(6, 7)
,
George Papaioannou
(3)
,
Virginie Eclache
(14)
,
Maria Dimou
(17)
,
Theodoros Iliakis
(17)
,
Rosa Collado
(18)
,
Michael Doubek
(6, 5, 7)
,
M. Jose Calasanz
(19)
,
Neus Ruiz-Xiville
(20)
,
Carolina Moreno
(21)
,
Marie Jarosova
(6, 5, 7)
,
Alexander Leeksma
(22, 23, 24)
,
Panayiotis Panayiotidis
(17)
,
Helena Podgornik
(25)
,
Florence Cymbalista
(14)
,
Achilles Anagnostopoulos
(3)
,
Livio Trentin
(11)
,
Niki Stavroyianni
(3)
,
Fred Davi
(8)
,
Paolo Ghia
(26)
,
Arnon Kater
(22, 23, 24)
,
Antonio Cuneo
(10)
,
Sarka Pospisilova
(6, 5, 7)
,
Blanca Espinet
(4)
,
Anastasia Athanasiadou
(3)
,
David Oscier
(9)
,
Claudia Haferlach
(2)
,
Kostas Stamatopoulos
(1, 12)
1
Uppsala University
2 MLL Münchner Leukämielabor GmbH / MLL Munich Leukemia Laboratory [Munich, Germany]
3 General Hospital of Thessaloniki George Papanikolaou
4 IMIM-Hospital del Mar
5 CEITEC MU - Central European Institute of Technology [Brno]
6 MUNI - Masaryk University [Brno]
7 University Hospital Brno
8 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
9 Royal Bournemouth Hospital
10 UniFE - Università degli Studi di Ferrara = University of Ferrara
11 Unipd - Università degli Studi di Padova = University of Padua
12 CERTH - Centre for Research and Technology Hellas
13 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
14 Hôpital Avicenne [AP-HP]
15 SIMHEL - Signalisation, Microenvironnement et Hémopathies Lymphoïdes B
16 Vall d'Hebron University Hospital [Barcelona]
17 NKUA - National and Kapodistrian University of Athens
18 Consorcio Hospital General Universitario de Valencia
19 UNAV - Universidad de Navarra [Pamplona]
20 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
21 Hospital de la Santa Creu i Sant Pau
22 AMC - Academic Medical Center - Academisch Medisch Centrum [Amsterdam]
23 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
24 A3I - Amsterdam institute for Infection and Immunity [Amsterdam, The Netherlands]
25 UMCL - University Medical Centre Ljubljana [Ljubljana, Slovenia]
26 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
2 MLL Münchner Leukämielabor GmbH / MLL Munich Leukemia Laboratory [Munich, Germany]
3 General Hospital of Thessaloniki George Papanikolaou
4 IMIM-Hospital del Mar
5 CEITEC MU - Central European Institute of Technology [Brno]
6 MUNI - Masaryk University [Brno]
7 University Hospital Brno
8 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
9 Royal Bournemouth Hospital
10 UniFE - Università degli Studi di Ferrara = University of Ferrara
11 Unipd - Università degli Studi di Padova = University of Padua
12 CERTH - Centre for Research and Technology Hellas
13 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
14 Hôpital Avicenne [AP-HP]
15 SIMHEL - Signalisation, Microenvironnement et Hémopathies Lymphoïdes B
16 Vall d'Hebron University Hospital [Barcelona]
17 NKUA - National and Kapodistrian University of Athens
18 Consorcio Hospital General Universitario de Valencia
19 UNAV - Universidad de Navarra [Pamplona]
20 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
21 Hospital de la Santa Creu i Sant Pau
22 AMC - Academic Medical Center - Academisch Medisch Centrum [Amsterdam]
23 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
24 A3I - Amsterdam institute for Infection and Immunity [Amsterdam, The Netherlands]
25 UMCL - University Medical Centre Ljubljana [Ljubljana, Slovenia]
26 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
Fanny Baran-Marszak
- Fonction : Auteur
- PersonId : 1216303
- IdHAL : fanny-baran-marszak
- ORCID : 0000-0002-3723-2927
Helena Podgornik
- Fonction : Auteur
- PersonId : 1217213
- ORCID : 0000-0003-3752-2067
Résumé
Abstract 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 +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.