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Acute Leukemias

In vivo apoptosis of CD8+ lymphocytes in acute myeloid leukemia patients: involvement of soluble HLA-I and Fas ligand

Leukemia volume 21, pages 253–260 (2007)Cite this article

Abstract

In this study, we show that high serum levels of soluble human leukocyte antigens (HLA) class I molecules (sHLA-I, range: 0.7–1.7 μg/ml) and soluble Fas ligand (FasL, range: 0.4–1.9 ng/ml) are detected in patients with acute myeloid leukemia (AML) at diagnosis, compared with healthy donors (HD) (sHLA-I, range: 0.1–0.6 μg/ml; sFasL, range: 0.1–0.4 ng/ml). Patients' sera were able to induce transcription and secretion of FasL in CD8+ T cells, followed by apoptosis in vitro; this apoptosis was inhibited by anti-HLA-I-specific monoclonal antibodies, suggesting that sHLA-I is responsible for cell death. These findings closely relate to the in vivo upregulation of FasL transcription observed in peripheral blood (PB) lymphocytes from AML patients; in the same cells, mRNA for the antiapoptotic proteins Bcl-2 and Bcl-xL was downregulated. Interestingly, caspase-8 and caspase-3, both downstream mediators of death receptor-induced apoptosis, were activated in CD8+ cells of AML patients; one-third of these cells were already apoptotic in vivo, at variance with lymphocytes of HD. These data strongly suggest that in AML, increased levels of sHLA-I molecules may contribute to the elimination of potentially anti-tumor effector cells through a FasL/Fas interaction.

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Acknowledgements

This work was partially supported by CIPE (IMM-03) and by the Italian Association for Cancer Research (to AP and MRZ).

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Authors and Affiliations

  1. Laboratory of Immunology, University of Genoa, Genoa, Italy

    P Contini

  2. Laboratory of Tumor Immunology, San Raffaele Scientific Institute, Milan, Italy

    M R Zocchi

  3. Clinical Hematology, University of Genoa, Genoa, Italy

    I Pierri & A Albarello

  4. Laboratory of Experimental Oncology D, National Institute for Cancer Research, Genoa, Italy

    A Poggi

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  1. P Contini
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  2. M R Zocchi
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  3. I Pierri
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  4. A Albarello
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Correspondence to M R Zocchi.

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Contini, P., Zocchi, M., Pierri, I. et al. In vivo apoptosis of CD8+ lymphocytes in acute myeloid leukemia patients: involvement of soluble HLA-I and Fas ligand. Leukemia 21, 253–260 (2007). https://doi.org/10.1038/sj.leu.2404494

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