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

Leukemia. 2007 Feb;21(2):253-60. doi: 10.1038/sj.leu.2404494. Epub 2006 Dec 14.

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 micro g/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 micro g/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-x(L) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • CD8-Positive T-Lymphocytes / immunology*
  • Enzyme Inhibitors / therapeutic use
  • Fas Ligand Protein / immunology*
  • Female
  • Histocompatibility Antigens Class I / immunology*
  • Histone Deacetylase Inhibitors
  • Humans
  • Leukemia, Myeloid / classification
  • Leukemia, Myeloid / drug therapy
  • Leukemia, Myeloid / genetics
  • Leukemia, Myeloid / immunology*
  • Male
  • Middle Aged
  • Valproic Acid / therapeutic use

Substances

  • Enzyme Inhibitors
  • Fas Ligand Protein
  • Histocompatibility Antigens Class I
  • Histone Deacetylase Inhibitors
  • Valproic Acid