Telomeric damage in early stage of CLL correlates with shelterin dysregulation

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BlankTelomeric damage in early stage of chronic lymphocytic leukemia correlates

with shelterin dysregulation.

A Augereau, C T'kint de Roodenbeke, T Simonet, S Bauwens, B Horard, M Callanan,

D Leroux, L Jallades, G Salles, E Gilson, and D Poncet

Blood, February 25, 2011;

Lyon-1 University, CNRS UMR 5239, Epigenetic and telomeric regulations, Lyon Sud

Medicine Faculty, Pierre Benite, France;

Cells of B-cell Chronic Lymphocytic Leukemia (B-CLL) are characterized by short

telomeres despite a low proliferative index. Since 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 B-CLL time

course. In a series restricted to 23 newly diagnosed Binet stage A CLL patients

compared to 12 healthy donors, we found a significant increase in recruitment of

DNA damage factors to telomeres showing telomere dysfunction in 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 two shelterin genes: ACD (coding for TPP1) (p=0.0464) and

TINF2 (coding for TIN2) (p=0.0177). We propose that telomeric deprotection in

early step of CLL is not merely the consequence of telomere shortening but also

of shelterin alteration.

PMID: 21355086