Oncotarget

Research Papers:

Karyotypic complexity rather than chromosome 8 abnormalities aggravates the outcome of chronic lymphocytic leukemia patients with TP53 aberrations

Gonzalo Blanco, Anna Puiggros, Panagiotis Baliakas, Anastasia Athanasiadou, MªDolores García-Malo, Rosa Collado, Aliki Xochelli, María Rodríguez-Rivera, Margarita Ortega, Mª José Calasanz, Elisa Luño, MªTeresa Vargas, Javier Grau, Carolina Martínez-Laperche, Alberto Valiente, José Cervera, Achilles Anagnostopoulos, Eva Gimeno, Eugènia Abella, Evangelia Stalika, Jesús Mª Hernández-Rivas, Francisco José Ortuño, Diego Robles, Ana Ferrer, David Ivars, Marcos González, Francesc Bosch, Pau Abrisqueta, Kostas Stamatopoulos and Blanca Espinet _

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Oncotarget. 2016; 7:80916-80924. https://doi.org/10.18632/oncotarget.13106

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Abstract

Gonzalo Blanco1,2,3, Anna Puiggros1,2, Panagiotis Baliakas4, Anastasia Athanasiadou5, MªDolores García-Malo6, Rosa Collado7, Aliki Xochelli4,8, María Rodríguez-Rivera1,2, Margarita Ortega9, Mª José Calasanz10, Elisa Luño11, MªTeresa Vargas12, Javier Grau13, Carolina Martínez-Laperche14, Alberto Valiente15, José Cervera16, Achilles Anagnostopoulos5, Eva Gimeno17, Eugènia Abella17, Evangelia Stalika8, Jesús Mª Hernández-Rivas18, Francisco José Ortuño6, Diego Robles19, Ana Ferrer1,2, David Ivars7, Marcos González18, Francesc Bosch9, Pau Abrisqueta9, Kostas Stamatopoulos4,5,8, Blanca Espinet1,2

1Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, Spain

2Grup de Recerca Translacional en Neoplàsies Hematològiques, Cancer Research Programme, IMIM-Hospital del Mar, Barcelona, Spain

3Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain

4Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden

5Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece

6Servicio de Hematología, Hospital Universitario Morales Meseguer, Murcia, Spain

7Servicio de Hematología, Consorcio Hospital General Universitario, Valencia, Spain

8Institute of Applied Biosciences, CERTH, Thessaloniki, Greece

9Laboratorio de Citogenética y Servicio de Hematología, Hospital Vall d'Hebron, Barcelona, Spain

10Servicio de Citogenética, Departamento de Genética, Universidad de Navarra, Pamplona, Spain

11Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain

12UGC de Hematología, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain

13Servei d’Hematologia, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona, Badalona, Spain

14Laboratorio de Genética Hematológica, Servicio de Hematología, Hospital G.U. Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain

15Servicios de Genética y Hematología, Complejo Hospitalario de Navarra, Pamplona, Spain

16Unidad de Genética, Hospital Universitario La Fe, Valencia, Spain

17Servei d’Hematologia, Hospital del Mar, Barcelona, Spain

18Servicio de Hematología, Hospital Universitario de Salamanca, IBSAL, IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca, CSIC, Salamanca, Spain

19Servicio de Hematología, Hospital Txagorritxu, Vitoria, Spain

Correspondence to:

Blanca Espinet, email: [email protected]

Keywords: CLL, TP53 aberrations, chromosome 8 abnormalities, complex karyotype, prognosis

Received: August 02, 2016     Accepted: October 27, 2016     Published: November 04, 2016

ABSTRACT

Patients with chronic lymphocytic leukemia (CLL) harboring TP53 aberrations (TP53abs; chromosome 17p deletion and/or TP53 mutation) exhibit an unfavorable clinical outcome. Chromosome 8 abnormalities, namely losses of 8p (8p−) and gains of 8q (8q+) have been suggested to aggravate the outcome of patients with TP53abs. However, the reported series were small, thus hindering definitive conclusions. To gain insight into this issue, we assessed a series of 101 CLL patients harboring TP53 disruption. The frequency of 8p− and 8q+ was 14.7% and 17.8% respectively. Both were associated with a significantly (P < 0.05) higher incidence of a complex karyotype (CK, ≥3 abnormalities) detected by chromosome banding analysis (CBA) compared to cases with normal 8p (N-8p) and 8q (N-8q), respectively. In univariate analysis for 10-year overall survival (OS), 8p− (P = 0.002), 8q+ (P = 0.012) and CK (P = 0.009) were associated with shorter OS. However, in multivariate analysis only CK (HR = 2.47, P = 0.027) maintained independent significance, being associated with a dismal outcome regardless of chromosome 8 abnormalities. In conclusion, our results highlight the association of chromosome 8 abnormalities with CK amongst CLL patients with TP53abs, while also revealing that CK can further aggravate the prognosis of this aggressive subgroup.


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