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

Autores: Blanco, G.; Puiggros, A.; Baliakas, P.; Athanasiadou, A.; García-Malo, M.; Collado, R.; Xochelli, A.; Rodríguez-Rivera, M.; Ortega, M.; Calasanz Abinzano, María José; Luño, E.; Vargas, M.; Grau, J.; Martínez-Laperche, C.; Valiente, A.; Cervera, J.; Anagnostopoulos, A.; Gimeno, E.; Abella, E.; Stalika, E.; Hernández-Rivas, J. M.; Ortuño, F. J.; Robles, D.; Ferrer, A.; Ivars, D.; González, M.; Bosch, F.; Abrisqueta, P.; Stamatopoulos, K.; Espinet, B.
Título de la revista: ONCOTARGET
ISSN: 1949-2553
Volumen: 7
Número: 49
Páginas: 80916 - 80924
Fecha de publicación: 2016
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.