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

Oncotarget. 2016 Dec 6;7(49):80916-80924. doi: 10.18632/oncotarget.13106.

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.

Keywords: CLL; TP53 aberrations; chromosome 8 abnormalities; complex karyotype; prognosis.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Chi-Square Distribution
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 8*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Kaplan-Meier Estimate
  • Karyotype*
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation
  • Phenotype
  • Proportional Hazards Models
  • Risk Factors
  • Spain
  • Time Factors
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Biomarkers, Tumor
  • TP53 protein, human
  • Tumor Suppressor Protein p53