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

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Blood First Edition Paper, prepublished online December 12, 2007; DOI

10.1182/blood-2007-09-111245.

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, t'Kint de Roodenbeke, Aude Roborel

de Climens, Elsa Ben Simon, Helene Merle-Beral, e Callet-Bauchu, Gilles

Salles, Laure Sabatier, Jozo Delic, and 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@... .

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