Changes in the expression of telomere maintenance genes suggest global telomere dysfunction in B-chronic lymphocytic leukemia.
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.
Poncet
Delphine
D
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.
Belleville
Aurélie
A
t'kint de Roodenbeke
Claire
C
Roborel de Climens
Aude
A
Ben Simon
Elsa
E
Merle-Beral
Hélène
H
Callet-Bauchu
Evelyne
E
Salles
Gilles
G
Sabatier
Laure
L
Delic
Jozo
J
Gilson
Eric
E
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
C495876:ACD protein, human; D018941:Antigens, CD19; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D019098:Telomerase