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

Blanco G, Puiggros A, Baliakas P, Athanasiadou A, García-Malo M, Collado R, Xochelli A, Rodríguez-Rivera M, Ortega M, Calasanz MJ, Luño E, Vargas M, Grau J, Martínez-Laperche C, Valiente A, Cervera J, Anagnostopoulos A, Gimeno E, Abella E, Stalika E, Hernández-Rivas JM, Ortuño FJ, Robles D, Ferrer A, Ivars D, González M, Bosch F, Abrisqueta P, Stamatopoulos K, Espinet B

Oncotarget 7 (49) 80916-80924 [2016-12-06; online 2016-11-09]

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.

Affiliated researcher

PubMed 27821812

DOI 10.18632/oncotarget.13106

Crossref 10.18632/oncotarget.13106

pii: 13106
pmc: PMC5348364