Research Papers:
Patients with chronic lymphocytic leukemia and complex karyotype show an adverse outcome even in absence of TP53/ATM FISH deletions
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Abstract
Anna Puiggros1,2, Rosa Collado3, Maria José Calasanz4, Margarita Ortega5, Neus Ruiz-Xivillé6, Alfredo Rivas-Delgado7, Elisa Luño8, Teresa González9, Blanca Navarro10, MaDolores García-Malo11, Alberto Valiente12, José Ángel Hernández13, María Teresa Ardanaz14, María Ángeles Piñan15, María Laura Blanco16, María Hernández-Sánchez17, Ana Batlle-López18, Rocío Salgado19, Marta Salido1,2, Ana Ferrer1,2, Pau Abrisqueta5, Eva Gimeno1, Eugènia Abella1, Christelle Ferrá6, María José Terol10, Francisco Ortuño11, Dolors Costa7, Carol Moreno16, Félix Carbonell3, Francesc Bosch5, Julio Delgado7 and Blanca Espinet1,2
1Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia i Servei Hematologia, Hospital del Mar, Barcelona, Spain
2Grup de Recerca Translacional en Neoplàsies Hematològiques, Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain
3Servicio de Hematología, Consorcio Hospital General Universitario, Valencia, Spain
4Servicio de Citogenética, Departamento de Genética, Universidad de Navarra, Pamplona, Spain
5Laboratorio de Citogenética y Servicio de Hematología, Hospital Vall d'Hebron, Barcelona, Spain
6Servei Laboratori Hematologia, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona, Badalona, Spain
7Secció d’Hematopatologia, Hospital Clínic, Institut d’Investigacions Biomèdiques Augustí Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
8Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain
9Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain
10Servicio de Hematología y Oncología Médica, Hospital Clínico Universitario de Valencia, Valencia, Spain
11Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, Murcia, Spain
12Servicios de Genética y Hematología, Complejo Hospitalario de Navarra, Pamplona, Spain
13Servicio de Hematología, Hospital Universitario Infanta Leonor, Madrid, Spain
14Servicio de Hematología, Hospital Txagorritxu, Vitoria, Spain
15Servicio de Hematología, Hospital de Cruces, Bilbao, Spain
16Servei d’Hematologia Hospital Universitari de la Santa Creu i Sant Pau, Barcelona, Spain
17Servicio de Hematología, Hospital Universitario de Salamanca, IBSAL, IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca, CSIC, Salamanca, Spain
18Servicio de Hematología, Hospital Universitario Marqués de Valdecilla, Santander, Spain
19Laboratorio de Citogenética, Servicio de Hematología, Fundación Jiménez Díaz, Madrid, Spain
Correspondence to:
Blanca Espinet, email: [email protected]
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.
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PII: 17350