Karyotypic complexity rather than chromosome 8 abnormalities aggravates the outcome of chronic lymphocytic leukemia patients with TP53 aberrations
Blanco, Gonzalo (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut)
Puiggros, Anna (Institut Hospital del Mar d'Investigacions Mèdiques)
Baliakas, Panagiotis (Uppsala University. Department of Immunology, Genetics and Pathology)
Athanasiadou, Anastasia (G. Papanicolaou Hospital (Thessaloniki, Greece))
García-Malo, MaDolores (Hospital General Universitario Morales Meseguer (Múrcia))
Collado, Rosa (Hospital General Universitario de Valencia)
Xochelli, Aliki (Institute of Applied Biosciences, CERTH, Thessaloniki, Greece)
Rodríguez-Rivera, María (Institut Hospital del Mar d'Investigacions Mèdiques)
Ortega, Margarita (Hospital Universitari Vall d'Hebron)
Calasanz, M.J (Universidad de Navarra. Departamento de Bioquímica y Genética)
Luño, Elisa (Hospital Universitario Central de Asturias)
Vargas, MªTeresa (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Grau Cat, Javier (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Martínez-Laperche, Carolina (Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM))
Valiente, Alberto (Complejo Hospitalario de Navarra)
Cervera, José (Hospital Universitari i Politècnic La Fe (València))
Anagnostopoulos, Achilles (George Papanicolaou General Hospital (Tessalònia, Grècia))
Gimeno, Eva (Hospital del Mar (Barcelona, Catalunya))
Abella Monreal, Eugenia (Hospital del Mar (Barcelona, Catalunya))
Stalika, Evangelia (Institute of Applied Biosciences, CERTH, Thessaloniki, Greece)
Hernández Rivas, Jesús María (Hospital Universitario de Salamanca)
Ortuño, Francisco José (Hospital General Universitario Morales Meseguer (Múrcia))
Robles, Diego (Servicio de Hematología, Hospital Txagorritxu, Vitoria, Spain)
Ferrer, Ana (Institut Hospital del Mar d'Investigacions Mèdiques)
Ivars, David (Hospital General Universitario de Valencia)
González, Marcos (Hospital Universitario de Salamanca. Centro de Investigación del Cáncer)
Bosch José, Francesc Xavier 1947- (Hospital Universitari Vall d'Hebron)
Abrisqueta, Pau (Hospital Universitari Vall d'Hebron)
Stamatopoulos, Kostas (Institute of Applied Biosciences, CERTH, Thessaloniki, Greece)
Espinet, Blanca (Institut Hospital del Mar d'Investigacions Mèdiques)
Universitat Autònoma de Barcelona

Fecha:	2016
Resumen:	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.
Ayudas:	Instituto de Salud Carlos III PI11-01621 Instituto de Salud Carlos III PI15-00437 Instituto de Salud Carlos III RD09/0076-00036 Instituto de Salud Carlos III RD12/0036-0044 Instituto de Salud Carlos III RD12/0036-0069 Instituto de Salud Carlos III PT13/0010-0005 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014-SGR58
Nota:	Altres ajuts: The authors want to thank Marta Salido, Carme Melero, Ana Batlle, Mª Ángeles Piñán, Alicia Rodríguez and George Papaioannou for their contribution to the study providing clinical or laboratory data, Sergi Mojal for statistical review, and Grupo Cooperativo Español de Citogenética Hematológica (GCECGH) and Grupo Español de Leucemia Linfática Crónica (GELLC). This work has been supported by "Xarxa de Bancs de tumors" sponsored by Pla Director d'Oncologia de Catalunya (XBTC) and Fundació La Caixa; the Swedish Cancer Society, the Swedish Research Council, the Lion's Cancer Research Foundation, and Selander's Foundation, Uppsala; H2020 "AEGLE, An analytics framework for integrated and personalized healthcare services in Europe" by the EU.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	CLL ; TP53 aberrations ; Chromosome 8 abnormalities ; Complex karyotype ; Prognosis
Publicado en:	Oncotarget, Vol. 7 (november 2016) , p. 80916-80924, ISSN 1949-2553

DOI: 10.18632/oncotarget.13106
PMID: 27821812

9 p, 809.0 KB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Instituto de Investigación contra la Leucemia Josep Carreras
Artículos > Artículos de investigación
Artículos > Artículos publicados