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

Gonzalo Blanco, Anna Puiggros, Panagiotis Baliakas, Anastasia Athanasiadou, Ma Dolores García-Malo, Rosa Collado, Aliki Xochelli, María Rodríguez-Rivera, Margarita Ortega, Ma José Calasanz, Elisa Luño, Ma Teresa Vargas, Javier Grau, Carolina Martínez-Laperche, Alberto Valiente, José Cervera, Achilles Anagnostopoulos, Eva Gimeno, Eugènia Abella, Evangelia StalikaJesús Ma Hernández-Rivas, Francisco José Ortuño, Diego Robles, Ana Ferrer, David Ivars, Marcos González, Francesc Bosch, Pau Abrisqueta, Kostas Stamatopoulos, Blanca Espinet

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)80916-80924
JournalOncotarget
Volume7
Issue number49
DOIs
Publication statusPublished - 1 Jan 2016

Keywords

  • Chromosome 8 abnormalities
  • CLL
  • Complex karyotype
  • Prognosis
  • TP53 aberrations

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