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

2016; Impact Journals LLC; Volume: 7; Issue: 49 Linguagem: Inglês

10.18632/oncotarget.13106

1949-2553

Gonzalo Blanco, Anna Puiggros, Panagiotis Baliakas, Anastasia Athanasiadou, MaDolores García-Malo, Rosa Collado, Aliki Xochelli, María Rodríguez‐Rivera, Margarita Ortega, Marı́a José Calasanz, Elisa Luño, MaTeresa Vargas, Javier Grau, Carolina Martínez‐Laperche, Alberto Valiente, José Cervera, Αchilles Anagnostopoulos, Eva Gimeno, Eugenia Abellá, Evangelia Stalika, José‐Ángel Hernández‐Rivas, Francisco José Ortuño, Diego Torrente Robles, Ana Ferrer, David Ivars, Marcos González, Francesc Bosch, Pau Abrisqueta, Κώστας Σταματόπουλος, Blanca Espinet,

Immunodeficiency and Autoimmune Disorders

// Gonzalo Blanco 1, 2, 3 , Anna Puiggros 1, 2 , Panagiotis Baliakas 4 , Anastasia Athanasiadou 5 , MªDolores García-Malo 6 , Rosa Collado 7 , Aliki Xochelli 4, 8 , María Rodríguez-Rivera 1, 2 , Margarita Ortega 9 , Mª José Calasanz 10 , Elisa Luño 11 , MªTeresa Vargas 12 , Javier Grau 13 , Carolina Martínez-Laperche 14 , Alberto Valiente 15 , José Cervera 16 , Achilles Anagnostopoulos 5 , Eva Gimeno 17 , Eugènia Abella 17 , Evangelia Stalika 8 , Jesús Mª Hernández-Rivas 18 , Francisco José Ortuño 6 , Diego Robles 19 , Ana Ferrer 1, 2 , David Ivars 7 , Marcos González 18 , Francesc Bosch 9 , Pau Abrisqueta 9 , Kostas Stamatopoulos 4, 5, 8 , Blanca Espinet 1, 2 1 Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, Spain 2 Grup de Recerca Translacional en Neoplàsies Hematològiques, Cancer Research Programme, IMIM-Hospital del Mar, Barcelona, Spain 3 Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain 4 Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden 5 Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece 6 Servicio de Hematología, Hospital Universitario Morales Meseguer, Murcia, Spain 7 Servicio de Hematología, Consorcio Hospital General Universitario, Valencia, Spain 8 Institute of Applied Biosciences, CERTH, Thessaloniki, Greece 9 Laboratorio de Citogenética y Servicio de Hematología, Hospital Vall d'Hebron, Barcelona, Spain 10 Servicio de Citogenética, Departamento de Genética, Universidad de Navarra, Pamplona, Spain 11 Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain 12 UGC de Hematología, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain 13 Servei d’Hematologia, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona, Badalona, Spain 14 Laboratorio de Genética Hematológica, Servicio de Hematología, Hospital G.U. Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain 15 Servicios de Genética y Hematología, Complejo Hospitalario de Navarra, Pamplona, Spain 16 Unidad de Genética, Hospital Universitario La Fe, Valencia, Spain 17 Servei d’Hematologia, Hospital del Mar, Barcelona, Spain 18 Servicio de Hematología, Hospital Universitario de Salamanca, IBSAL, IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca, CSIC, Salamanca, Spain 19 Servicio de Hematología, Hospital Txagorritxu, Vitoria, Spain Correspondence to: Blanca Espinet, email: bespinet@parcdesalutmar.cat 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 ( TP53 abs; 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 TP53 abs. 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 TP53 abs, while also revealing that CK can further aggravate the prognosis of this aggressive subgroup.