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

Autor:	Blanco G; Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, Spain.; Grup de Recerca Translacional en Neoplàsies Hematològiques, Cancer Research Programme, IMIM-Hospital del Mar, Barcelona, Spain.; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain., Puiggros A; Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, Spain.; Grup de Recerca Translacional en Neoplàsies Hematològiques, Cancer Research Programme, IMIM-Hospital del Mar, Barcelona, Spain., Baliakas P; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Athanasiadou A; Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece., García-Malo M; Servicio de Hematología, Hospital Universitario Morales Meseguer, Murcia, Spain., Collado R; Servicio de Hematología, Consorcio Hospital General Universitario, Valencia, Spain., Xochelli A; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.; Institute of Applied Biosciences, CERTH, Thessaloniki, Greece., Rodríguez-Rivera M; Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, Spain.; Grup de Recerca Translacional en Neoplàsies Hematològiques, Cancer Research Programme, IMIM-Hospital del Mar, Barcelona, Spain., Ortega M; Laboratorio de Citogenética y Servicio de Hematología, Hospital Vall d'Hebron, Barcelona, Spain., Calasanz MJ; Servicio de Citogenética, Departamento de Genética, Universidad de Navarra, Pamplona, Spain., Luño E; Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain., Vargas M; UGC de Hematología, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain., Grau J; Servei d'Hematologia, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona, Badalona, Spain., Martínez-Laperche C; Laboratorio de Genética Hematológica, Servicio de Hematología, Hospital G.U. Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain., Valiente A; Servicios de Genética y Hematología, Complejo Hospitalario de Navarra, Pamplona, Spain., Cervera J; Unidad de Genética, Hospital Universitario La Fe, Valencia, Spain., Anagnostopoulos A; Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece., Gimeno E; Servei d'Hematologia, Hospital del Mar, Barcelona, Spain., Abella E; Servei d'Hematologia, Hospital del Mar, Barcelona, Spain., Stalika E; Institute of Applied Biosciences, CERTH, Thessaloniki, Greece., Hernández-Rivas JM; Servicio de Hematología, Hospital Universitario de Salamanca, IBSAL, IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca, CSIC, Salamanca, Spain., Ortuño FJ; Servicio de Hematología, Hospital Universitario Morales Meseguer, Murcia, Spain., Robles D; Servicio de Hematología, Hospital Txagorritxu, Vitoria, Spain., Ferrer A; Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, Spain.; Grup de Recerca Translacional en Neoplàsies Hematològiques, Cancer Research Programme, IMIM-Hospital del Mar, Barcelona, Spain., Ivars D; Servicio de Hematología, Consorcio Hospital General Universitario, Valencia, Spain., González M; Servicio de Hematología, Hospital Universitario de Salamanca, IBSAL, IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca, CSIC, Salamanca, Spain., Bosch F; Laboratorio de Citogenética y Servicio de Hematología, Hospital Vall d'Hebron, Barcelona, Spain., Abrisqueta P; Laboratorio de Citogenética y Servicio de Hematología, Hospital Vall d'Hebron, Barcelona, Spain., Stamatopoulos K; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.; Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece.; Institute of Applied Biosciences, CERTH, Thessaloniki, Greece., Espinet B; Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, Spain.; Grup de Recerca Translacional en Neoplàsies Hematològiques, Cancer Research Programme, IMIM-Hospital del Mar, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2016 Dec 06; Vol. 7 (49), pp. 80916-80924.
DOI:	10.18632/oncotarget.13106
Abstrakt:	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.
Databáze:	MEDLINE
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