Oncotarget

Research Papers:

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

Anna Puiggros, Rosa Collado, Maria José Calasanz, Margarita Ortega, Neus Ruiz-Xivillé, Alfredo Rivas-Delgado, Elisa Luño, Teresa González, Blanca Navarro, MaDolores García-Malo, Alberto Valiente, José Ángel Hernández, María Teresa Ardanaz, María Ángeles Piñan, María Laura Blanco, María Hernández-Sánchez, Ana Batlle-López, Rocío Salgado, Marta Salido, Ana Ferrer, Pau Abrisqueta, Eva Gimeno, Eugènia Abella, Christelle Ferrá, María José Terol, Francisco Ortuño, Dolors Costa, Carol Moreno, Félix Carbonell, Francesc Bosch, Julio Delgado and Blanca Espinet _

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Oncotarget. 2017; 8:54297-54303. https://doi.org/10.18632/oncotarget.17350

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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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