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Acute Lymphoblastic Leukemia

Modification of topoisomerase genes copy number in newly diagnosed childhood acute lymphoblastic leukemia

Leukemia volume 17, pages 532–540 (2003)Cite this article

Abstract

Topoisomerase genes were analyzed at both DNA and RNA levels in 25 cases of newly diagnosed childhood acute lymphoblastic leukemia (ALL). The results of molecular analysis were compared to risk group classification of children in order to identify molecular characteristics associated with response to therapy. At diagnosis, allelic imbalance at topo-isomerase IIα (TOP2A) gene locus was found in 75% of informative cases whereas topoisomerase I and IIβ gene loci are altered in none or only one case, respectively. By semi-quantitative Polymerase chain reaction, we found a 2.5 to 8-fold TOP2A gene amplification in 72% of the children, which was correlated to gene overexpression in every case. These results show that TOP2A gene amplification is a frequent event in ALL at diagnosis. Interestingly, we also identified a small population of children that do not present TOP2A gene amplification or gene overexpression and who are significantly associated with very high risk classified patients showing glucocorticoid resistance. In conclusion, characterization of TOP2A gene status in childhood ALL at diagnosis provides useful complementary information for risk assessment.

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Acknowledgements

We thank Eliane Mengus and Evelyne Neuville for expert technical assistance as well as Guy Hamel and Nicolas Meyer for helpful discussions and statistical analysis. Research grants: Supported by the Ligue Régionale contre le Cancer (Comité du Bas-Rhin et du Haut-Rhin), the ARAME (Association régionale d'action médicale et sociale en faveur d'enfants atteints d'affection maligne) and the Hôpitaux Universitaires de Strasbourg

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Authors and Affiliations

  1. Laboratoire de Biochimie et de Biologie Moléculaire Hôital de Hautepierre, Strasbourg, France

    E Guérin, E Pencreac'h, A Schneider, A-C Voegeli, M-P Gaub & P Oudet

  2. INSERM U381, Strasbourg, France

    E Guérin & M-P Gaub

  3. Service d'Onco-Hématologie Pédiatrique Hôpital de Hautepierre, Strasbourg, France

    N Entz-Werlé, D Eyer, F Uettwiller, A Babin & P Lutz

  4. Laboratoire Hospitalier d'Hématologie Biologique Hôpital de Hautepierre, Strasbourg, France

    A Falkenrodt & M Lessard

  5. INSERM U184, Illkirch, France

    A-C Voegeli & P Oudet

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Guérin, E., Entz-Werlé, N., Eyer, D. et al. Modification of topoisomerase genes copy number in newly diagnosed childhood acute lymphoblastic leukemia. Leukemia 17, 532–540 (2003). https://doi.org/10.1038/sj.leu.2402774

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