Predisposition to therapy-related acute leukemia with balanced chromosomal translocations does not result from a major constitutive defect in DNA double-strand break end joining |
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Authors: | Coiteux Valérie Onclercq-Delic Rosine Fenaux Pierre Amor-Guéret Mounira |
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Institution: | Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8126, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94 805 Villejuif Cedex, France. |
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Abstract: | The frequency of acute myeloid leukemia (AML) with balanced chromosomal translocations arising after anticancer therapy with DNA-damaging agents such as DNA topoisomerase II inhibitors has increased over the last two decades. However, factors that predispose to these therapy-related disorders are still poorly defined. It has been reported that DNA double-strand break (DSB) repair by the non-homologous end-joining (NHEJ) pathway is impaired in myeloid leukemia cells. This led us to hypothesize that therapy-related AML (t-AML) may result from individual differences in the repair of DSBs generated by the treatment. We show here that DSB repair is accurate, in vivo, in non-tumoral cells derived from patients who developed t-AML with t(9;11) or t(15;17) translocation after treatment for a first cancer with DNA topoisomerase II inhibitors. These results indicate that a major constitutive defect in the NHEJ pathway is unlikely to predispose to t-AML with balanced chromosomal translocations. |
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