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Telomeric damage in early stage of chronic lymphocytic leukemia correlates with shelterin dysregulation

Abstract : Cells of B-cell chronic lymphocytic leukemia (B-CLL) are characterized by short telomeres despite a low proliferative index. Because telomere length has been reported to be a valuable prognosis criteria, there is a great interest in a deep understanding of the origin and consequences of telomere dysfunction in this pathology. Cases of chromosome fusion involving extremely short telomeres have been reported at advanced stage. In the present study, we address the question of the existence of early telomere dysfunction during the B-CLL time course. In a series restricted to 23 newly diagnosed Binet stage A CLL patients compared with 12 healthy donors, we found a significant increase in recruitment of DNA-damage factors to telomeres showing telomere dysfunction in the early stage of the disease. Remarkably, the presence of dysfunctional telomeres did not correlate with telomere shortening or chromatin marks deregulation but with a down-regulation of 2 shelterin genes: ACD (coding for TPP1; P = .0464) and TINF2 (coding for TIN2; P = .0177). We propose that telomeric deprotection in the early step of CLL is not merely the consequence of telomere shortening but also of shelterin alteration.
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Submitted on : Friday, April 5, 2013 - 3:09:14 PM
Last modification on : Monday, April 25, 2022 - 3:48:01 PM


  • HAL Id : ensl-00808485, version 1



Adeline Augereau, Claire t'Kint de Roodenbeke, Thomas Simonet, Serge Bauwens, Béatrice Horard, et al.. Telomeric damage in early stage of chronic lymphocytic leukemia correlates with shelterin dysregulation. Blood, American Society of Hematology, 2011, 118 (5), pp.1316-1322. ⟨ensl-00808485⟩



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