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Title

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

AuthorsBlanco, Gonzalo; Puiggros, Anna; Baliakas, Panagiotis; Athanasiadou, Anastasia; García-Malo, Mª Dolores; Collado, Rosa; Xochelli, Aliki; Rodríguez-Rivera, María; Ortega, Margarita; Calasanz, Mª Jose; Luño, Elisa; Vargas, Mª Teresa; Grau, Javier; Martínez-Laperche, Carolina; Valiente, Alberto; Cervera, José; Anagnostopoulos, Achilles; Gimeno, Eva; Abella, Eugènia; Stalika, Evangelia; Hernández, Jesús M. ; Ortuño, Francisco José; Robles, Diego; Ferrer, Ana; Ivars, David; González, Marcos ; Bosch, Francesc; Abrisqueta, Pau; Stamatopoulos, Kostas; Espinet, Blanca
KeywordsCLL
TP53 aberrations
Chromosome 8 abnormalities
Complex karyotype
Prognosis
Issue Date2016
PublisherImpact Journals
CitationOncotarget 7(49): 80916-80924 (2016)
AbstractPatients 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.
Publisher version (URL)https://doi.org/10.18632/oncotarget.13106
URIhttp://hdl.handle.net/10261/168581
DOIhttp://dx.doi.org/10.18632/oncotarget.13106
Identifiersdoi: 10.18632/oncotarget.13106
e-issn: 1949-2553
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