title: Changes in the expression of telomere maintenance genes suggest global telomere dysfunction in B-chronic lymphocytic leukemia.
abstract: 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.
authors: Laboratoire de Biologie Moleculaire et de Cellule, Centre National de la Recherche Scientifique UMR5239, IFR128, Faculté de Médecine Lyon Sud, Université Lyon 1, Lyon, France.
authors: Delphine
authors: D
authors: Poncet
authors: Aurélie
authors: A
authors: Belleville
authors: Claire
authors: C
authors: t'kint de Roodenbeke
authors: Aude
authors: A
authors: Roborel de Climens
authors: Elsa
authors: E
authors: Ben Simon
authors: Hélène
authors: H
authors: Merle-Beral
authors: Evelyne
authors: E
authors: Callet-Bauchu
authors: Gilles
authors: G
authors: Salles
authors: Laure
authors: L
authors: Sabatier
authors: Jozo
authors: J
authors: Delic
authors: Eric
authors: E
authors: Gilson
mesh_terms: D018941:Antigens, CD19 / Q000097:blood; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D000089804:Shelterin Complex; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000235:genetics* / Q000648:ultrastructure; D034501:Telomere-Binding Proteins
chemical_list: C495876:ACD protein, human; D018941:Antigens, CD19; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D019098:Telomerase