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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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NEOPLASIA

Brief Report

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

Delphine Poncet1,2, Aurélie Belleville1,2, Claire t'Kint de Roodenbeke1, Aude Roborel de Climens1, Elsa Ben Simon1, Hélène Merle-Beral3, Evelyne Callet-Bauchu1,4, Gilles Salles1,4, Laure Sabatier5, Jozo Delic5, and Eric Gilson1,2

1 Laboratoire de Biologie Moleculaire et de Cellule (LBMC), Centre National de la Recherche Scientifique (CNRS) UMR5239, IFR128, Faculté de Médecine Lyon Sud, Université Lyon 1, Lyon; 2 Service de Biologie des Tumeurs, Hôpital Lyon-Sud, Hospices Civils de Lyon, Lyon; 3 Service d'Hématologie Biologique, Groupe Hospitalier Pitié-Salpêtrière, Paris; 4 Service d'Hématologie, Hôpital Lyon-Sud, Hospices Civils de Lyon, Lyon; and 5 Laboratoire d'OncoHématologie, Centre d'Etude Atomique, Institut de Radiobiologie Cellulaire et Moleculaire, Fontenay-aux-Roses, France

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 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 2-fold reduced (P < .001), contrasting with the higher expression of TPP1 and RPA1 (P < .001). This differential expression pattern suggests that both telomerase down-regulation and changes in telomeric proteins composition are involved in the pathogenesis of B-CLL.


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