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 Blood, 15 February 2008, Vol. 111, No. 4, pp. 2388-2391.
Prepublished online as a Blood First Edition Paper on December 12, 2007; DOI 10.1182/blood-2007-09-111245.

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Submitted September 6, 2007
Accepted December 6, 2007

Changes in the expression of telomere maintenance genes suggest global telomere dysfunction in B chronic lymphocytic leukemia

Delphine Poncet, Aurelie Belleville, Claire t'Kint de Roodenbeke, Aude Roborel de Climens, Elsa Ben Simon, Helene Merle-Beral, Evelyne Callet-Bauchu, Gilles Salles, Laure Sabatier, Jozo Delic, and Eric Gilson*

LBMC, CNRS UMR5239, IFR128, Faculte de Medecine Lyon Sud, Universite Lyon, Lyon, France
Service de Biologie des Tumeurs, Hopital Lyon-Sud, Hospices Civils de Lyon, Lyon, France
Service d'Hematologie Biologique, Groupe Hospitalier Pitie-Salpetriere, Paris, France
Service d'Hematologie, Hopital Lyon-Sud, Hospices Civils de Lyon, Lyon, France
Laboratoire d'Onco-Hematologie, CEA/iRCM, Fontenay-aux-Roses Cedex, France

* Corresponding author; email: eric.gilson{at}ens-lyon.fr.

In this study, we explored the telomeric changes that occur in B-Chronic Lymphocytic Leukemia (B-CLL), in which telomere length has recently been demonstrated to be a powerful prognostic marker. We carried out a transcriptomic analysis of telomerase components (hTERT and Dyskerin), shelterin proteins (TRF1, TRF2, hRAP1, TIN2, POT1 and TPP1) and of a set of multifunctional proteins involved in telomere maintenance (hEST1A, MRE11, RAD50, Ku80 and RPA1) in peripheral B-cells from 42 B-CLL patients and 20 healthy donors. We found that in B-CLL cells, the expressions of hTERT, Dyskerin, TRF1, hRAP1, POT1, hEST1A, MRE11, RAD50 and Ku80 were more than twofold reduced (p<0.001), contrasting with the higher expression of TPP1 and RPA1 (p<0.001). This differential expression pattern suggests that both telomerase downregulation and changes in telomeric proteins composition are involved in the pathogenesis of B-CLL


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