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

Adeline Augereau; Claire t'Kint de Roodenbeke; Thomas Simonet; Serge Bauwens; Béatrice Horard; Mary Callanan; Dominique Leroux; Laurent Jallades; Gilles Salles; Eric Gilson; Delphine Poncet

Journal articles

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

Adeline Augereau ^{1, 2} Claire t'Kint de Roodenbeke ¹ Thomas Simonet ¹ Serge Bauwens ¹ Béatrice Horard ¹ Mary Callanan ³ Dominique Leroux ^{4, 5} Laurent Jallades ⁶ Gilles Salles ^{1, 7} Eric Gilson ^{1, 2, 7, 8} Delphine Poncet ^{1, 7}

1 LBMC - Laboratoire de Biologie Moléculaire de la Cellule

2 Laboratory of Biology and Pathology of Genomes

3 INSERM U823, équipe 7 (Voies Oncogéniques Des Hémopathies Malignes)

INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble, UJF - Université Joseph Fourier - Grenoble 1

4 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble

5 UJF - Université Joseph Fourier - Grenoble 1

6 Laboratoire d'Hématologie

7 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]

8 CHU de Nice

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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Human health and pathology / Hematology

Complete list of metadata

https://hal-ens-lyon.archives-ouvertes.fr/ensl-03510946
Contributor : Adeline Augereau Connect in order to contact the contributor
Submitted on : Tuesday, January 4, 2022 - 4:46:29 PM
Last modification on : Wednesday, January 5, 2022 - 3:48:39 AM

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

Identifiers

Collections

Citation

Export

Metrics

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

Identifiers

Collections

Citation

Export

Share

Metrics