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Acute Non Lymphocytic Leukemias

Telomerase targeting by retinoids in cells from patients with myeloid leukemias of various subtypes, not only APL

Leukemia volume 20, pages 599–603 (2006)Cite this article

Abstract

Numerous strategies have been proposed to specifically inhibit telomerase (human telomerase reverse transcriptase (hTERT)) but to date only a few are clinically relevant in anticancer therapy. Recently, we have shown that long-term treatment with all-trans retinoic acid (ATRA), a compound clinically approved for differentiation therapy of acute promyelocytic leukemia (APL), represses hTERT in differentiation-resistant APL cell lines leading to telomere shortening and death. This signaling requires the co-activation of the retinoic acid receptor α (RARα) and the retinoic X receptor (RXR). In contrast to differentiation-therapy, which is only successful in this subtype of leukemia, the telomerase-targeted pathway could also be of use in non-APL. Here, we demonstrate that repression of hTERT occurs in fresh blasts cells from patients with myeloid leukemias of various subtypes exposed ex vivo to ATRA or synthetic retinoids. These results support the idea that, by hTERT targeting, retinoids can induce telomere shortening and cell death and their integration in therapy protocols for myeloid leukemias refractory to maturation should be considered.

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Acknowledgements

This work was supported by INSERM, the Association pour la Recherche contre le Cancer (ARC nos. 3416). FP was funded by the Fondation pour la Recherche Médicale (FRM), International Agency for Research on Cancer (IARC) and European Commission (Marie Curie Intra-European fellowship). CD is a research fellow of Association pour la Recherche contre le Cancer. We are indebted to Dr Marc Maynadie (Service d'Hématologie Biologique 21000 Dijon, France) and Dr Loïc Fouillard (Département d'hématologie et de Thérapie Cellulaire, Hôpital Saint-Antoine, Paris, France) for providing some of the patient samples, to Dr Nedime Serakinci and Dr Eigil Kjeldsen, (Aarhus, Denmark) for helpful discussions at the beginning of the project, to Pr Eric Solary (INSERM U517, IFR 100, Faculté de Médecine, 21000 Dijon, France) and Dr Bodil Bjørndal, (Department of Molecular Biology, University of Bergen, Norway) for critical reading of the manuscript.

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Author notes

  1. F Pendino and J Hillion: These authors contributed equally to this work.

Authors and Affiliations

  1. INSERM U685, Hôpital Saint-Louis, Paris, France

    F Pendino, J Hillion, C Dudognon, M Lanotte & E Ségal-Bendirdjian

  2. Département d'Hématologie, CHU Hotel Dieu, Nantes, France

    J Delaunay

  3. INSERM U716, Laboratoire de Pharmacologie, AP-HP, Hôpital Saint-Louis, Paris, France

    S Mourah & M-P Podgorniak

  4. INSERM U517, IFR 100, Faculté de Médecine, Dijon, France

    I Lafon

  5. Département d'Hématologie, Hôpital Saint-Louis, Paris, France

    C Chomienne & H Dombret

  6. Centre d'Investigation Clinique, Hôpital Saint-Louis, Paris, France

    P Rousselot

  7. Service d'Hématologie, Hôpital Mignot, Le Chesnay Cedex, France

    P Rousselot

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  1. F Pendino
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  2. J Hillion
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  3. C Dudognon
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  8. C Chomienne
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  9. M Lanotte
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  12. E Ségal-Bendirdjian
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Correspondence to E Ségal-Bendirdjian.

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Pendino, F., Hillion, J., Dudognon, C. et al. Telomerase targeting by retinoids in cells from patients with myeloid leukemias of various subtypes, not only APL. Leukemia 20, 599–603 (2006). https://doi.org/10.1038/sj.leu.2404127

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  • DOI: https://doi.org/10.1038/sj.leu.2404127

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