Telomeres and prognosis in patients with chronic lymphocytic leukaemia
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.
KeywordsCLL Prognostic factors IGHV mutations Telomeres Telomerase
We thank Anja Führer, Songül Basoglu, Barbara Friedmann, Andrea Kopplin, and Ute Schmücker for their expert technical assistance. This work was supported by a grant from the Bernese Cancer League (G.M.B.) and from the IFORES program of the University Duisburg Essen (L.S.).
Conflict of interest
The other authors declare no competing financial interests.
- 11.Verfaillie CM, Pera MF, Lansdorp PM. Stem cells: hype and reality. Hematol Am Soc Hematol Educ Program. 2002;1:369–91.Google Scholar
- 35.Rossi D, Lobetti BC, Genuardi E, Monitillo L, Drandi D, Cerri M, et al. Telomere length is an independent predictor of survival, treatment requirement and Richter’s syndrome transformation in chronic lymphocytic leukemia. Leukemia. 2009;218:122–30.Google Scholar