Intratumoral genetic heterogeneity and number of cytogenetic aberrations provide additional prognostic significance in chronic lymphocytic leukemia

Genet Med. 2017 Feb;19(2):182-191. doi: 10.1038/gim.2016.81. Epub 2016 Jul 28.

Abstract

Purpose: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with cytogenetic aberrations that are still considered the gold standard of prognostic factors. However, heterogeneity remains within each cytogenetic group, especially in patients with concomitant cytogenetic aberrations.

Methods: A panel of DNA probes was used to detect cytogenetic aberrations, including RB1/D13S25 at 13q14, ATM at 11q22, TP53 at 17p13, CEP12 and IGH translocation at 14q32, by fluorescence in situ hybridization. A comprehensive method integrating the number of cytogenetic aberrations and intratumoral genetic heterogeneity was used to analyze the prognosis for patients with concomitant aberrations.

Results: Within the conventional favorable or neutral prognostic groups (i.e., with del 13q, trisomy 12, and/or t(14q32)), the coincidence of these three aberrations worsened survival in terms of time to first therapy, progression-free survival, and overall survival. However, within the conventional unfavorable prognostic group (i.e., del 11q or del 17p), patients with a minor unfavorable clone had an unexpected survival advantage compared with patients with a major unfavorable clone. A new cytogenetic prognostic system that integrates the number of cytogenetic aberrations and intratumoral genetic subclones was more precise than the conventional system.

Conclusion: The number of cytogenetic aberrations and the size of intratumoral genetic subclones should be comprehensively considered to determine the prognosis for CLL.Genet Med 19 2, 182-191.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chromosome Aberrations
  • Chromosome Deletion
  • Cytogenetic Analysis / methods
  • Disease-Free Survival
  • Female
  • Genetic Heterogeneity*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / physiopathology
  • Male
  • Middle Aged
  • Prognosis*
  • Translocation, Genetic / genetics*