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Telomere dysfunction accurately predicts clinical outcome in chronic lymphocytic leukaemia, even in patients with early stage disease

Lookup NU author(s): Professor James Allan


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Defining the prognosis of individual cancer sufferers remains a significant clinical challenge. Here we assessed the ability of high-resolution single telomere length analysis (STELA), combined with an experimentally derived definition of telomere dysfunction, to predict the clinical outcome of patients with chronic lymphocytic leukaemia (CLL). We defined the upper telomere length threshold at which telomere fusions occur and then used the mean of the telomere fusogenic' range as a prognostic tool. Patients with telomeres within the fusogenic range had a significantly shorter overall survival (P<00001; Hazard ratio [HR]=132, 95% confidence interval [CI]=116-1064) and this was preserved in early-stage disease patients (P<00001, HR=193, 95% CI=178-8025). Indeed, our assay allowed the accurate stratification of Binet stage A patients into those with indolent disease (91% survival at 10years) and those with poor prognosis (13% survival at 10years). Furthermore, patients with telomeres above the fusogenic mean showed superior prognosis regardless of their IGHV mutation status or cytogenetic risk group. In keeping with this finding, telomere dysfunction was the dominant variable in multivariate analysis. Taken together, this study provides compelling evidence for the use of high-resolution telomere length analysis coupled with a definition of telomere dysfunction in the prognostic assessment of CLL.

Publication metadata

Author(s): Lin TT, Norris K, Heppel NH, Pratt G, Allan JM, Allsup DJ, Bailey J, Cawkwell L, Hills R, Grimstead JW, Jones RE, Britt-Compton B, Fegan C, Baird DM, Pepper C

Publication type: Article

Publication status: Published

Journal: British Journal of Haematology

Year: 2014

Volume: 167

Issue: 2

Pages: 214-223

Print publication date: 01/10/2014

Online publication date: 03/07/2014

ISSN (print): 0007-1048

ISSN (electronic): 1365-2141

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1111/bjh.13023


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Funder referenceFunder name
National Institute for Social Care and Health Research (NISCHR) through Cancer Genetics Biomedical Research Unit
10003Leukaemia & Lymphoma Research
11006Leukaemia & Lymphoma Research
11024Leukaemia & Lymphoma Research
8044Leukaemia & Lymphoma Research
C17199/A13490Cancer Research UK