Short telomeres are associated with inferior outcome, genomic complexity, and clonal evolution in chronic lymphocytic leukemia. Academic Article uri icon

Overview

abstract

  • Telomere length in chronic lymphocytic leukemia (CLL) has been shown to be of prognostic importance, but the analyses have largely been executed on heterogeneous patient cohorts outside of clinical trials. In the present study, we performed a comprehensive analysis of telomere length associations in the well characterized CLL8 trial (n = 620) of the German CLL study group, with validation in a representative cohort of the CLL4 trial (n = 293). Absolute telomere length was analyzed using quantitative-PCR. Apart from identifying associations of short telomere length with adverse prognostic factors and survival, the study identified cases with 17p- and 11q- associated with TP53 and ATM loss, respectively, to have the shortest telomeres, even when these aberrations were present in small subclones. Thus, telomere shortening may precede acquisition of the high-risk aberrations, contributing to disease evolution. In line with this, telomere shortening was associated with an increase in genomic complexity as well as clonal evolution, highlighting its importance as a biomarker especially in monitoring disease progression in non-high-risk CLL.

authors

  • Jebaraj, Billy Michael Chelliah
  • Tausch, Eugen
  • Landau, Dan Avi
  • Bahlo, Jasmin
  • Robrecht, Sandra
  • Taylor-Weiner, Amaro N
  • Bloehdorn, Johannes
  • Scheffold, Annika
  • Mertens, Daniel
  • Böttcher, Sebastian
  • Kneba, Michael
  • Jäger, Ulrich
  • Zenz, Thorsten
  • Wenger, Michael K
  • Fingerle-Rowson, Guenter
  • Wendtner, Clemens
  • Fink, Anna-Maria
  • Wu, Catherine J
  • Eichhorst, Barbara
  • Fischer, Kirsten
  • Hallek, Michael
  • Döhner, Hartmut
  • Stilgenbauer, Stephan

publication date

  • March 25, 2019

Research

keywords

  • Clonal Evolution
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Telomere
  • Telomere Shortening

Identity

PubMed Central ID

  • PMC6737251

Scopus Document Identifier

  • 85063526677

Digital Object Identifier (DOI)

  • 10.1038/s41375-019-0446-4

PubMed ID

  • 30911113

Additional Document Info

volume

  • 33

issue

  • 9