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On the TRAIL of a new therapy for leukemia

Leukemia volume 19, pages 2195–2202 (2005)Cite this article

Abstract

The cytokine TRAIL (tumor necrosis factor α-related apoptosis-inducing ligand) as well as agonistic antibodies that bind to the TRAIL receptors, death receptor 4 (DR4) and DR5, are undergoing preclinical and early clinical evaluation as potential therapeutic agents for a variety of hematological and nonhematological malignancies. Here, we briefly review the normal biological function of TRAIL, the mechanism of cytotoxicity of TRAIL receptor ligands, and their effects on normal myeloid progenitors, myelodysplastic marrow and leukemic cells, including acute myelogenous leukemia (AML) and chronic lymphocytic leukemia (CLL), in vitro. Recent observations suggesting that DR4 is the predominant receptor for the cytotoxic effects of TRAIL in CLL and that histone deacetylase inhibitors synergize with TRAIL in CLL in vitro are described and discussed. Collectively, the reviewed studies not only illustrate the potential therapeutic usefulness of TRAIL and the agonistic antibodies, but also highlight the need for additional preclinical evaluation of these agents.

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Acknowledgements

Studies in the our laboratory were supported in part by R01 CA69008. Helpful discussions with Gregory Gores and editorial assistance of Deb Strauss are gratefully acknowledged.

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA

    S H Kaufmann & D P Steensma

  2. Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN, USA

    S H Kaufmann

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  1. S H Kaufmann
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  2. D P Steensma
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Correspondence to S H Kaufmann.

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Kaufmann, S., Steensma, D. On the TRAIL of a new therapy for leukemia. Leukemia 19, 2195–2202 (2005). https://doi.org/10.1038/sj.leu.2403946

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  • DOI: https://doi.org/10.1038/sj.leu.2403946

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