International Journal of Hematology

, Volume 93, Issue 1, pp 74–82

Telomeres and prognosis in patients with chronic lymphocytic leukaemia

  • Ludger Sellmann
  • Dirk de Beer
  • Marius Bartels
  • Bertram Opalka
  • Holger Nückel
  • Ulrich Dührsen
  • Jan Dürig
  • Marc Seifert
  • Dörte Siemer
  • Ralf Küppers
  • Gabriela M. Baerlocher
  • Alexander Röth
Original Article

DOI: 10.1007/s12185-010-0750-2

Cite this article as:
Sellmann, L., de Beer, D., Bartels, M. et al. Int J Hematol (2011) 93: 74. doi:10.1007/s12185-010-0750-2

Abstract

In the present study, telomere length, telomerase activity, the mutation load of immunoglobulin variable heavy chain (IGHV) genes, and established prognostic factors were investigated in 78 patients with chronic lymphocytic leukaemia (CLL) to determine the impact of telomere biology on the pathogenesis of CLL. Telomere length was measured by an automated multi-colour flow-FISH, and an age-independent delta telomere length (ΔTL) was calculated. CLL with unmutated IGHV genes was associated with shorter telomeres (p = 0.002). Furthermore, we observed a linear correlation between the frequency of IGHV gene mutations and elongation of telomeres (r = 0.509, p < 0.001). With respect to prognosis, a threshold ΔTL of −4.2 kb was the best predictor for progression-free and overall survival. ΔTL was not significantly altered over time or with therapy. The correlation between the mutational load in IGHV genes and the ΔTL in CLL might reflect the initial telomere length of the putative cell of origin (pre- versus post-germinal center B cells). In conclusion, the ΔTL is a reliable prognostic marker for patients with CLL. Short telomeres and high telomerase activity as occurs in some patients with CLL with a worse prognosis might be an ideal target for treatment with telomerase inhibitors.

Keywords

CLLPrognostic factorsIGHV mutationsTelomeresTelomerase

Supplementary material

12185_2010_750_MOESM1_ESM.doc (50 kb)
Supplementary material 1 (DOC 49 kb)

Copyright information

© The Japanese Society of Hematology 2010

Authors and Affiliations

  • Ludger Sellmann
    • 1
    • 2
    • 5
  • Dirk de Beer
    • 3
  • Marius Bartels
    • 1
  • Bertram Opalka
    • 1
  • Holger Nückel
    • 1
  • Ulrich Dührsen
    • 1
  • Jan Dürig
    • 1
  • Marc Seifert
    • 2
  • Dörte Siemer
    • 2
  • Ralf Küppers
    • 2
  • Gabriela M. Baerlocher
    • 3
    • 4
  • Alexander Röth
    • 1
  1. 1.Department of HaematologyUniversity of Duisburg EssenEssenGermany
  2. 2.Institute of Cell Biology (Cancer Research)University of Duisburg EssenEssenGermany
  3. 3.Experimental Haematology, Department of Clinical ResearchUniversity of BernBernSwitzerland
  4. 4.Department of HaematologyUniversity Hospital BernBernSwitzerland
  5. 5.Department of HaematologyUniversity HospitalEssenGermany