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Prevalence and clinical significance of resistance to perforin- and FAS-mediated cell death in leukemia

Leukemia volume 18, pages 1401–1405 (2004)Cite this article

Abstract

Killer lymphocytes play a central therapeutic role in graft-versus-leukemia following allogeneic hematopoietic stem cell transplantation (HSCT). The Perforin/Granzyme and FAS/CD95 pathways are of crucial importance in tumor cell elimination by killer cells. In this study, we have examined whether hematological malignancies are resistant to perforin and anti-FAS antibodies. Leukemic cells were studied from 29 patients suffering either from acute or chronic myeloid leukemia (AML or CML), acute or chronic lymphoid leukemia, or non-Hodgkin's lymphoma. An average of 49 vs 5% of specific cell killing was found when using perforin vs anti-FAS antibodies, respectively. Interestingly, resistance towards both perforin and anti-FAS antibodies was found exclusively in leukemic cells from patients with myeloid leukemia. Analysis of leukemic cells from patients with CML, suffering from leukemia relapse after HSCT and given donor lymphocyte infusion (DLI) to induce remission, indicated that the effectiveness of treatment with DLI was not associated with sensitivity of leukemic cells to perforin. In conclusion, resistance towards anti-FAS antibodies is a common phenomenon in leukemia/lymphoma, whereas perforin resistance occurs only in myeloid leukemia. However, as a single parameter, perforin resistance does not appear to be suitable to predict the outcome of DLI.

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Acknowledgements

This work was supported by grants from the Vanderes and Bekales foundations. We thank Dr A Bloem from the Department of Medical Immunology for his helpful advice on FACS analysis.

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Authors and Affiliations

  1. Department of Hematology, Jordan Laboratory for Hemato-Oncology, University Medical Center Utrecht, Utrecht, The Netherlands

    H G Otten, W G J van Ginkel, A Hagenbeek & E J Petersen

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  1. H G Otten
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  2. W G J van Ginkel
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  3. A Hagenbeek
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  4. E J Petersen
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Correspondence to H G Otten.

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Financial support for this study was provided by the Vanderes and Bekales foundations

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Otten, H., van Ginkel, W., Hagenbeek, A. et al. Prevalence and clinical significance of resistance to perforin- and FAS-mediated cell death in leukemia. Leukemia 18, 1401–1405 (2004). https://doi.org/10.1038/sj.leu.2403414

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