Patients with chronic lymphocytic leukemia and complex karyotype show an adverse outcome even in absence of TP53/ATM FISH deletions

Genomic complexity identified by chromosome banding analysis (CBA) predicts a worse clinical outcome in CLL patients treated either with standard or new treatments. Herein, we analyzed the clinical impact of complex karyotypes (CK) with or without high-risk FISH deletions (ATM and/or TP53, HR-FISH)...

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Autores: Puiggros, Anna|||0000-0001-9627-4978, Collado, Rosa|||0000-0002-8205-6192, Calasanz, M.J|||0000-0002-0374-3008, Ortega, Margarita, Ruiz-Xivillé, Neus, Rivas-Delgado, Alfredo|||0000-0003-0385-3415, Luño, Elisa, González, Teresa, Navarro, Blanca, García-Malo, MaDolores, Valiente, Alberto, Hernández, José Ángel, Ardanaz, María Teresa, Piñan, María Ángeles, Blanco, María Laura, Hernández-Sánchez, María|||0000-0001-9968-2782, Batlle Lopez, Ana|||0000-0003-4143-9020, Salgado Sánchez, Rocío Nieves|||0000-0003-1678-8982, Salido, Marta|||0000-0001-9988-5977, Ferrer, Ana, Abrisqueta, Pau|||0000-0001-9625-7422, Gimeno, Eva|||0000-0002-3534-6189, Abella Monreal, Eugenia|||0000-0001-9605-8458, Ferrá, Christelle|||0000-0003-4571-5125, Terol, María José, Ortuño, Francisco José|||0000-0003-4450-9346, Costa, Dolors|||0000-0002-8276-3292, Moreno, Carol|||0000-0003-3275-0271, Carbonell, Félix, Bosch Albareda, Francesc|||0000-0001-9241-2886, Delgado, Julio|||0000-0002-5157-4376, Espinet i Solà, Blanca
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:186329
Acceso en línea:https://ddd.uab.cat/record/186329
https://dx.doi.org/urn:doi:10.18632/oncotarget.17350
Access Level:acceso abierto
Palabra clave:CLL
Complex karyotype
ATM deletion
TP53 deletion
Descripción
Sumario:Genomic complexity identified by chromosome banding analysis (CBA) predicts a worse clinical outcome in CLL patients treated either with standard or new treatments. Herein, we analyzed the clinical impact of complex karyotypes (CK) with or without high-risk FISH deletions (ATM and/or TP53, HR-FISH) in a cohort of 1045 untreated MBL/CLL patients. In all, 99/1045 (9.5%) patients displayed a CK. Despite ATM and TP53 deletions were more common in CK (25% vs 7%; P < 0.001; 40% vs 5%; P < 0.001, respectively), only 44% (40/90) patients with TP53 deletions showed a CK. CK group showed a significant higher two-year cumulative incidence of treatment (48% vs 20%; P < 0.001), as well as a shorter overall survival (OS) (79 mo vs not reached; P < 0.001). When patients were categorized regarding CK and HR-FISH, those with both characteristics showed the worst median OS (52 mo) being clearly distinct from those non-CK and non-HR-FISH (median not reached), but no significant differences were detected between cases with only CK or HR-FISH. Both CK and TP53 deletion remained statistically significant in the multivariate analysis for OS. In conclusion, CK group is globally associated with advanced disease and poor prognostic markers. Further investigation in larger cohorts with CK lacking HR-FISH is needed to elucidate which mechanisms underlie the poor outcome of this subgroup.

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