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

Blood. 2008 Feb 15;111(4):2388-91. doi: 10.1182/blood-2007-09-111245. Epub 2007 Dec 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD19 / blood
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / enzymology
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Mutation
  • Shelterin Complex
  • Telomerase / genetics*
  • Telomere / genetics*
  • Telomere / ultrastructure
  • Telomere-Binding Proteins

Substances

  • ACD protein, human
  • Antigens, CD19
  • Shelterin Complex
  • Telomere-Binding Proteins
  • Telomerase