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

2017; Impact Journals LLC; Volume: 8; Issue: 33 Linguagem: Inglês

10.18632/oncotarget.17350

1949-2553

Anna Puiggros, Rosa Collado, Marı́a José Calasanz, Margarita Ortega, Neus Ruiz‐Xivillé, Alfredo Rivas‐Delgado, Elisa Luño, Teresa González, Blanca Navarro, MaDolores García-Malo, Alberto Valiente, José‐Ángel Hernández‐Rivas, María T. Ardañaz, M.A. Piñán, María Laura Blanco, María Hernández‐Sánchez, Ana Batlle‐López, Rocío Salgado, Marta Salido, Ana Ferrer, Pau Abrisqueta, Eva Gimeno, Eugenia Abellá, Christelle Ferrà, María José Terol, Francisco José Ortuño, Dolors Costa, Carol Moreno, Félix Carbonell, Francesc Bosch, Julio Delgado, Blanca Espinet,

Immunodeficiency and Autoimmune Disorders

// Anna Puiggros 1, 2 , Rosa Collado 3 , Maria José Calasanz 4 , Margarita Ortega 5 , Neus Ruiz-Xivillé 6 , Alfredo Rivas-Delgado 7 , Elisa Luño 8 , Teresa González 9 , Blanca Navarro 10 , MaDolores García-Malo 11 , Alberto Valiente 12 , José Ángel Hernández 13 , María Teresa Ardanaz 14 , María Ángeles Piñan 15 , María Laura Blanco 16 , María Hernández-Sánchez 17 , Ana Batlle-López 18 , Rocío Salgado 19 , Marta Salido 1, 2 , Ana Ferrer 1, 2 , Pau Abrisqueta 5 , Eva Gimeno 1 , Eugènia Abella 1 , Christelle Ferrá 6 , María José Terol 10 , Francisco Ortuño 11 , Dolors Costa 7 , Carol Moreno 16 , Félix Carbonell 3 , Francesc Bosch 5 , Julio Delgado 7 and Blanca Espinet 1, 2 1 Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia i Servei Hematologia, Hospital del Mar, Barcelona, Spain 2 Grup de Recerca Translacional en Neoplàsies Hematològiques, Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain 3 Servicio de Hematología, Consorcio Hospital General Universitario, Valencia, Spain 4 Servicio de Citogenética, Departamento de Genética, Universidad de Navarra, Pamplona, Spain 5 Laboratorio de Citogenética y Servicio de Hematología, Hospital Vall d'Hebron, Barcelona, Spain 6 Servei Laboratori Hematologia, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona, Badalona, Spain 7 Secció d’Hematopatologia, Hospital Clínic, Institut d’Investigacions Biomèdiques Augustí Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain 8 Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain 9 Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain 10 Servicio de Hematología y Oncología Médica, Hospital Clínico Universitario de Valencia, Valencia, Spain 11 Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain 12 Servicios de Genética y Hematología, Complejo Hospitalario de Navarra, Pamplona, Spain 13 Servicio de Hematología, Hospital Universitario Infanta Leonor, Madrid, Spain 14 Servicio de Hematología, Hospital Txagorritxu, Vitoria, Spain 15 Servicio de Hematología, Hospital de Cruces, Bilbao, Spain 16 Servei d’Hematologia Hospital Universitari de la Santa Creu i Sant Pau, Barcelona, Spain 17 Servicio de Hematología, Hospital Universitario de Salamanca, IBSAL, IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca, CSIC, Salamanca, Spain 18 Servicio de Hematología, Hospital Universitario Marqués de Valdecilla, Santander, Spain 19 Laboratorio de Citogenética, Servicio de Hematología, Fundación Jiménez Díaz, Madrid, Spain Correspondence to: Blanca Espinet, email: bespinet@parcdesalutmar.cat Keywords: CLL, complex karyotype, ATM deletion, TP53 deletion Received: March 03, 2017 Accepted: April 11, 2017 Published: April 21, 2017 ABSTRACT 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.