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Sola dosis facit venenum. Leukemia in gene therapy trials: a question of vectors, inserts and dosage?

Leukemia volume 22, pages 1849–1852 (2008)Cite this article

Abstract

In clinical gene therapy trials for X-linked severe combined immunodeficiency, the development of leukemia has come up as a severe adverse effect. In all five cases, T-cell acute lymphoblastic leukemia (T-ALL) occurred as a direct consequence of insertional mutagenesis by the retrovirus used to deliver the therapeutic gene. Here, we review the mechanisms of insertional mutagenesis, the fuction of the Il2RG gene and the future developments in the field. New lentiviral and γ retroviral vectors can significantly improve the safety profile of the tools used but still carry the risk of insertional mutagenesis, as shown in this issue of Leukemia. Finally, the unfortunate side effects of gene therapy have given more insight into the development of human T-ALL.

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Authors and Affiliations

  1. Department of Immunology, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands

    F J T Staal, K Pike-Overzet, Y Y Ng & J J M van Dongen

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  1. F J T Staal
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  2. K Pike-Overzet
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  3. Y Y Ng
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  4. J J M van Dongen
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Correspondence to F J T Staal.

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Staal, F., Pike-Overzet, K., Ng, Y. et al. Sola dosis facit venenum. Leukemia in gene therapy trials: a question of vectors, inserts and dosage?. Leukemia 22, 1849–1852 (2008). https://doi.org/10.1038/leu.2008.219

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