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Chronic Lymphocytic Leukemia

Telomerase expression in B-cell chronic lymphocytic leukemia predicts survival and delineates subgroups of patients with the same igVH mutation status and different outcome

Leukemia volume 21, pages 965–972 (2007)Cite this article

Abstract

Activation of telomerase reverse transcriptase (hTERT) is essential for unlimited cell growth and plays a critical role in tumorigenesis. We investigated hTERT gene expression in 134 B-cell chronic lymphocytic leukemia (B-CLL) cases and evaluated its prognostic value with other prognostic markers (IgVH mutation status, CD38 and ZAP-70 expression). Real-time PCR assays to quantify either all hTERT transcripts (AT) or only the full length (FL) transcript encoding the functional protein were developed. hTERT-AT levels strongly correlated with hTERT-FT levels (r=0.743, P<0.0001); both inversely correlated with the percentage of IgVH mutation (P<0.005) and were significantly higher in unmutated than in mutated cases (P=0.004 and P=0.001, respectively). The hTERT values which best discriminated between the unmutated and mutated IgVH cases were 150 and 40 copies for hTERT-AT and hTERT-FL, respectively. Using these cut-off values, there was a significant difference in the survival of patients with high or low hTERT levels (P<0.0001). Unmutated cases with low hTERT levels had an overall survival close to mutated cases with high hTERT levels. Thus, this work identifies hTERT-RNA level as a new prognostic marker in B-CLL, and may be used to identify previously unrecognized patient groups with the same IgVH mutation status and different disease outcomes.

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Acknowledgements

This work was supported by the Italian Association for Cancer Research (AIRC, Milan), by the MURST (Rome) and by Fondazione Berlucchi (Brescia). The authors wish to thank M Donach for his help in the preparation of this paper.

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Author notes

  1. L Terrin and L Trentin: These authors equally contributed to the work

Authors and Affiliations

  1. Department of Oncology and Surgical Sciences, Section of Oncology, University of Padua, Padua, Italy

    L Terrin, I Corradini & A De Rossi

  2. Istituto Oncologico Veneto, IRCCS, Padua, Italy

    L Terrin & R Bertorelle

  3. Department of Clinical and Experimental Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, University of Padua, Padua, Italy

    L Trentin, P Carli, N Maschio, F Noventa & G Semenzato

  4. Clinical and Experimental Hematology Research Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy

    M Degan, M D Bo & V Gattei

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Correspondence to A De Rossi.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Terrin, L., Trentin, L., Degan, M. et al. Telomerase expression in B-cell chronic lymphocytic leukemia predicts survival and delineates subgroups of patients with the same igVH mutation status and different outcome. Leukemia 21, 965–972 (2007). https://doi.org/10.1038/sj.leu.2404607

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