Original Article

International Journal of Hematology

, Volume 93, Issue 1, pp 74-82

Telomeres and prognosis in patients with chronic lymphocytic leukaemia

  • Ludger SellmannAffiliated withDepartment of Haematology, University of Duisburg EssenInstitute of Cell Biology (Cancer Research), University of Duisburg EssenDepartment of Haematology, University Hospital Email author 
  • , Dirk de BeerAffiliated withExperimental Haematology, Department of Clinical Research, University of Bern
  • , Marius BartelsAffiliated withDepartment of Haematology, University of Duisburg Essen
  • , Bertram OpalkaAffiliated withDepartment of Haematology, University of Duisburg Essen
  • , Holger NückelAffiliated withDepartment of Haematology, University of Duisburg Essen
  • , Ulrich DührsenAffiliated withDepartment of Haematology, University of Duisburg Essen
  • , Jan DürigAffiliated withDepartment of Haematology, University of Duisburg Essen
  • , Marc SeifertAffiliated withInstitute of Cell Biology (Cancer Research), University of Duisburg Essen
  • , Dörte SiemerAffiliated withInstitute of Cell Biology (Cancer Research), University of Duisburg Essen
    • , Ralf KüppersAffiliated withInstitute of Cell Biology (Cancer Research), University of Duisburg Essen
    • , Gabriela M. BaerlocherAffiliated withExperimental Haematology, Department of Clinical Research, University of BernDepartment of Haematology, University Hospital Bern
    • , Alexander RöthAffiliated withDepartment of Haematology, University of Duisburg Essen

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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

CLL Prognostic factors IGHV mutations Telomeres Telomerase