Abstract
Telomere length (TL) has been associated with outcome in chronic lymphocytic leukemia (CLL). The aim of this extensive analysis carried out on 401 CLL patients was to assess TL conclusively as a prognostic biomarker. Our study included two cohorts used as learning (191 patients) and blinded validation series (210 patients). A TL cutoff of 5000 bp was chosen by receiver operating characteristic (ROC) analysis and Youden's index in the learning series. In this series, TL⩽5000 bp was independently associated to a worse outcome for both overall survival (OS; 105.5 vs 281 months, P<0.001) and treatment-free survival (TFS; 24.6 vs 73 months, P<0.001). In the blinded validation series, TL⩽5000 bp was confirmed as an independent outcome predictor for OS (79.8 vs not reached, P<0.001) and TFS (15.2 vs 130.8 months, P<0.001). Moreover, TL⩽5000 bp independently predicted the risk of Richter's syndrome (5-year risk: 18.9 vs 6.4%, P=0.016). Within CLL subsets defined by biological predictors, TL consistently identified patient subgroups harboring unfavorable prognosis. These results demonstrate that TL is a powerful independent predictor of multiple outcomes in CLL, and contributes to refine the prognostic assessment of this disease when utilized in combination with other prognostic markers. We thus believe that this prognostic biomarker has the potential for a more widespread use in CLL.
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Acknowledgements
This work was supported in part by Compagnia di San Paolo (Torino, Italy), Ministero Italiano Universitá e Ricerca (MIUR) (PRIN 2006 and Ricerca locale), Rome, Italy; by Fondazione Neoplasie del sangue (FO. NE. SA), Torino Italy; Ricerca Sanitaria Finalizzata, Regione Piemonte, Torino, Italy; Progetto Alfieri—Fondazione CRT, Torino, Italy; Novara-AIL Onlus, Novara, Italy; Associazione Franca Capurro per Novara Onlus, Novara, Italy.
We thank Antonella Fiorillo for secretarial support.
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Contributions: M Ladetto designed and performed research, supervised laboratory experiments, analyzed data and wrote the paper. D Rossi performed research, analyzed data, performed statistical analysis and wrote the paper. G Gaidano designed and performed research, analyzed data and wrote the paper. C Lobetti Bodoni performed research, made laboratory experiments, collected clinical information, analyzed data and wrote the paper. R Passera performed statistical analysis. E Genuardi, L Monitillo, D Drandi, M Cerri, C Deambrogi, I Ricca, A Rocci, S Ferrero, E Bernocco, D Capello, L De Paoli, M Boi and P Omedè made laboratory experiments. L Bergui provided patient samples and clinical information. M Massaia, C Tarella and M Boccadoro provided critical organizational support.
Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)
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Rossi, D., Lobetti Bodoni, C., Genuardi, E. et al. Telomere length is an independent predictor of survival, treatment requirement and Richter's syndrome transformation in chronic lymphocytic leukemia. Leukemia 23, 1062–1072 (2009). https://doi.org/10.1038/leu.2008.399
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DOI: https://doi.org/10.1038/leu.2008.399
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