Supported by grants from Société Française du Cancer, Société Française d'Hématologie, Ligue Nationale contre le Cancer, Association pour la Recherche sur le Cancer and Commissariat à l'Energie Atomique.
Mutagenicity of non-homologous end joining DNA repair in a resistant subset of human chronic lymphocytic leukaemia B cells
Article first published online: 20 MAR 2006
British Journal of Haematology
Volume 133, Issue 5, pages 520–525, June 2006
How to Cite
Deriano, L., Merle-Béral, H., Guipaud, O., Sabatier, L. and Delic, J. (2006), Mutagenicity of non-homologous end joining DNA repair in a resistant subset of human chronic lymphocytic leukaemia B cells. British Journal of Haematology, 133: 520–525. doi: 10.1111/j.1365-2141.2006.06071.x
- Issue published online: 27 APR 2006
- Article first published online: 20 MAR 2006
- Received 6 December 2005; accepted for publication 1 February 2006
- B-chronic lymphocytic leukaemia;
- non-homologous end joining DNA repair;
- genotoxic resistance
Non-homologous end joining (NHEJ) is an important determinant of genomic stability in mammalian cells. This DNA repair pathway is upregulated in a subset of B-cell chronic lymphocytic leukaemia (B-CLL) cells resistant to DNA damage-induced apoptosis. Using an in vitro assay for double-strand breaks (DSB) end ligation, we studied the fidelity of DSB repair in B-CLL cells which were resistant or sensitive to in vitro DSB-induced apoptosis with concomitant patients’ resistance or sensitivity to chemotherapy, respectively. The fidelity of DNA repair was determined by DNA sequencing of polymerase chain reaction products cloned in pGEM-T vector. Sequence analysis of DNA end junctions showed that the frequency of accurate ligation was higher in sensitive B-CLL cells and control cell lines, than in resistant cells where end joining was associated with extended deletions. Upregulated and error-prone NHEJ in resistant cells could be a quite possible mechanism underlying both genomic instability and poor clinical outcome.