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HTLV 1-Adult T Cell Leukemia

Evidence against a direct cytotoxic effect of alpha interferon and zidovudine in HTLV-I associated adult T cell leukemia/lymphoma

Leukemia volume 14, pages 716–721 (2000)Cite this article

Abstract

The combination of the anti-viral agents, zidovudine (AZT) and interferon-α (IFN), is a potent treatment of HTLV-I-associated adult T cell leukemia/lymphoma (ATL). In this study we investigate the possible mechanism of action of this combination by examining several cellular parameters including cell proliferation, cell cycle distribution and apoptosis. The ATL-derived T cell lines HuT-102 and MT-2 served as models. HTLV-I negative T cell lines (CEM and Jurkat) were used as controls. No significant modification of cell growth was observed except at suprapharmacological doses of AZT and IFN. Moreover, these effects were less pronounced in HTLV-I-infected cell lines compared to control cell lines. AZT and IFN treatment did not induce any significant modification of the expression of bcl-2 and p53. Interestingly no in vitrocytotoxic effect of AZT/IFN combination was observed on fresh leukemic cells derived from an acute ATL patient at diagnosis despite achievement of in vivo complete remission using the same therapy. These results suggest that the therapeutic effect of AZT and IFN is not through a direct cytotoxic effect of these drugs on the leukemic cells.

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Acknowledgements

This project is supported by grants from the American University of Beirut Medical Practice Plan, the Lebanese National Research Council and the ‘Programme Frano-Libanais CEDRE’. The excellent technical assistance of the American University of Beirut Core Laboratory Facilities personnel is greatly appreciated.

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Authors and Affiliations

  1. Department of Internal Medicine, American University of Beirut, Beirut, Lebanon

    A Bazarbachi & R Nasr

  2. Department of Biochemistry, American University of Beirut, Beirut, Lebanon

    A Bazarbachi, R Nasr, N Darwiche & G Dbaibo

  3. Department of Human Morphology, American University of Beirut, Beirut, Lebanon

    ME El-Sabban

  4. CHU de Pointe à Pitre, Guadeloupe, France

    A Mahé

  5. Institut Pasteur, Paris, France

    R Mahieux & A Gessain

  6. Department of Pediatrics, American University of Beirut, Beirut, Lebanon

    G Dbaibo

  7. CNRS URA 1461, Necker Hospital, Paris, France

    J Kersual & O Hermine

  8. UPR 9051 CNRS, Hôpital Saint-Louis, Paris, France

    Y Zermati, L Dianoux, MK Chelbi-Alix & H de Thé

  9. Department of Hematology, Necker Hospital, Paris

    O Hermine

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  1. A Bazarbachi
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Bazarbachi, A., Nasr, R., El-Sabban, M. et al. Evidence against a direct cytotoxic effect of alpha interferon and zidovudine in HTLV-I associated adult T cell leukemia/lymphoma. Leukemia 14, 716–721 (2000). https://doi.org/10.1038/sj.leu.2401742

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