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

P. Contini, M. R. Zocchi, I. Pierri, A. Albarello, A. Poggi

Research output: Contribution to journalArticle

Abstract

In this study, we show that high serum levels of soluble human leukocyte antigens (HLA) class I molecules (sHLA-I, range: 0.7-1.7μg/ml) and soluble Fas ligand (FasL, range: 0.4-1.9ng/ml) are detected in patients with acute myeloid leukemia (AML) at diagnosis, compared with healthy donors (HD) (sHLA-I, range: 0.1-0.6μg/ml; sFasL, range: 0.1-0.4ng/ 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.

Original languageEnglish
Pages (from-to)253-260
Number of pages8
JournalLeukemia
Volume21
Issue number2
DOIs
Publication statusPublished - Feb 2007

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

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