ATM aberrations in chronic lymphocytic leukemia: del(11q) rather than ATM mutations is an adverse-prognostic biomarker

[EN]Despite the well-established adverse impact of del(11q) in chronic lymphocytic leukemia (CLL), the prognostic significance of somatic ATM mutations remains uncertain. We evaluated the effects of ATM aberrations (del(11q) and/or ATM mutations) on time-to-first-treatment (TTFT) in 3631 untreated p...

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Detalhes bibliográficos
Autores: Thorvaldsdottir, Birna, Mansouri, Larry, Sutton, Lesley-Ann, Nadeu, Ferran, Meggendorfer, Manja, Parker, Helen, Brieghel, Christian, Laidou, Stamatia, Moia, Riccardo, Rossi, Davide, Kotaskova, Jana, Delgado, Julio, Rodríguez Vicente, Ana E., Benito Sánchez, Rocío, Rigolin, Gian Matteo, Bonfiglio, Silvia, Scarfò, Lydia, Mattsson, Mattias, Davis, Zadie, Baliakas, Panagiotis, Rapado, Inmaculada, Miras, Fatima, Martinez-Lopez, Joaquín, de la Serna, Javier, Hernández Rivas, Jesús María, Larráyoz, María José, Calasanz, María José, Smedby, Karin E, Espinet, Blanca, Puiggros, Anna, Bullinger, Lars, Bosch, Francesc, Tazón-Vega, Bárbara, Baran-Marszak, Fanny, Oscier, David, Nguyen-Khac, Florence, Zenz, Thorsten, Terol, Maria Jose, Cuneo, Antonio, Hernández-Sánchez, María, Pospisilova, Sarka, Gaidano, Gianluca, Niemann, Carsten U, Campo, Elias, Strefford, Jonathan C, Ghia, Paolo, Stamatopoulos, Kostas, Rosenquist, Richard
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:dnet:gredos______::d1c21fb5b84fd45c90cc6669160844c8
Acesso em linha:http://hdl.handle.net/10366/171560
Access Level:acceso abierto
Palavra-chave:Ataxia Telangiectasia Mutated Proteins
Leukemia, Lymphocytic, Chronic, B-Cell
Mutation
Biomarkers, Tumor
Chromosome Deletion
Chromosomes, Human, Pair 11
Humans
Prognosis
Male
Female
Middle Aged
Aged
Aged, 80 and over
Adult
Chromosomes
Leukemia
24 Ciencias de la Vida
pronóstico
proteínas mutadas de ataxia telangiectasia
deleción cromosómica
adulto
humanos
mutación
anciano
mediana edad
leucemia
cromosomas
Descrição
Resumo:[EN]Despite the well-established adverse impact of del(11q) in chronic lymphocytic leukemia (CLL), the prognostic significance of somatic ATM mutations remains uncertain. We evaluated the effects of ATM aberrations (del(11q) and/or ATM mutations) on time-to-first-treatment (TTFT) in 3631 untreated patients with CLL, in the context of IGHV gene mutational status and mutations in nine CLL-related genes. ATM mutations were present in 246 cases (6.8%), frequently co-occurring with del(11q) (112/246 cases, 45.5%). ATM-mutated patients displayed a different spectrum of genetic abnormalities when comparing IGHV-mutated (M-CLL) and unmutated (U-CLL) cases: M-CLL was enriched for SF3B1 and NFKBIE mutations, whereas U-CLL showed mutual exclusivity with trisomy 12 and TP53 mutations. Isolated ATM mutations were rare, affecting 1.2% of Binet A patients and <1% of M-CLL cases. While univariable analysis revealed shorter TTFT for Binet A patients with any ATM aberration compared to ATM-wildtype, multivariable analysis identified only del(11q), trisomy 12, SF3B1, and EGR2 mutations as independent prognosticators of shorter TTFT among Binet A patients and within M-CLL and U-CLL subgroups. These findings highlight del(11q), and not ATM mutations, as a key biomarker of increased risk of early progression and need for therapy, particularly in otherwise indolent M-CLL, providing insights into risk-stratification and therapeutic decision-making.

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