Telomere dysfunction-induced foci arise with the onset of telomeric deletions and complex chromosomal aberrations in resistant chronic lymphocytic leukemia cells.

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BlankTelomere dysfunction-induced foci arise with the onset of telomeric

deletions and complex chromosomal aberrations in resistant chronic lymphocytic

leukemia cells.

Blood. 2010 Apr 27;

Authors: Brugat T, Nguyen-Khac F, Grelier A, Merle-Béral H, Delic J

In somatic cells, eroded telomeres can induce DNA double-strand break (DSB)

signaling leading to a form of replicative senescence or apoptosis, both of

which are barriers to tumorigenesis. However, cancer cells might display

telomere dysfunctions which in conjunction with defects in DNA repair and

apoptosis, enables them to circumvent these pathways. Chronic lymphocytic

leukemia (CLL) cells exhibit telomere dysfunction and a subset of these cells

are resistant to DNA damage-induced apoptosis and display short telomeres. We

show here that these cells exhibit significant resection of their protective

telomeric 3' single-stranded overhangs and an increased number of

telomere-induced foci (TIF) containing gammaH2AX and 53BP1. Chromatin

immunoprecipitation and immunofluorescence experiments demonstrated increased

levels of telomeric Ku70 and phospho-S2056-DNA-PKcs, two essential components of

the mammalian non-homologous end-joining DNA repair system. Notably, these CLL

cells display deletions of telomeric signals on one or two chromatids in

parallel with 11q22 deletions, or with 13q14 deletions associated with another

chromosomal aberration or with a complex karyotype. Taken together, our results

indicate that a subset of CLL cells from patients with an unfavorable clinical

outcome harbor a novel type of chromosomal aberration due to telomere

dysfunction.

PMID: 20424183 [PubMed - as supplied by publisher]