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Updated: Aug 6, 2026

Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells
Published on: February 24, 2014
Predisposition to therapy-related acute leukemia with balanced chromosomal translocations does not result from a
Valérie Coiteux1, Rosine Onclercq-Delic, Pierre Fenaux
1Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8126, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94 805 Villejuif Cedex, France.
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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