Telomeres and prognosis in patients with chronic lymphocytic leukaemia

Sellmann, Ludger; de Beer, Dirk; Bartels, Marius; Opalka, Bertram; Nückel, Holger; Dührsen, Ulrich; Dürig, Jan; Seifert, Marc; Siemer, Dörte; Küppers, Ralf; Baerlocher, Gabriela M; Röth, Alexander (2011). Telomeres and prognosis in patients with chronic lymphocytic leukaemia. International journal of hematology, 93(1), pp. 74-82. Tokyo: Springer 10.1007/s12185-010-0750-2

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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 ( TL) 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 TL of -4.2 kb was the best predictor for progression-free and overall survival. TL was not significantly altered over time or with therapy. The correlation between the mutational load in IGHV genes and the TL in CLL might reflect the initial telomere length of the putative cell of origin (pre- versus post-germinal center B cells). In conclusion, the TL 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory

UniBE Contributor:

Baerlocher, Gabriela M.

ISSN:

0925-5710

Publisher:

Springer

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:08

Last Modified:

17 Mar 2015 19:09

Publisher DOI:

10.1007/s12185-010-0750-2

PubMed ID:

21203871

Web of Science ID:

000288027400012

URI:

https://boris.unibe.ch/id/eprint/668 (FactScience: 200339)

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