Indoleamine 2,3-dioxygenase activity of acute myeloid leukemia cells can be measured from patients' sera by HPLC and is inducible by IFN-gamma

Leuk Res. 2009 Mar;33(3):490-4. doi: 10.1016/j.leukres.2008.06.014. Epub 2008 Jul 18.

Abstract

The enzyme indoleamine 2,3-dioxygenase (IDO) converts tryptophan to kynurenine, blocking T-cell activation and inducing immunosuppression. In patients with acute myeloid leukemia (AML), the serum kynurenine/tryptophan ratio (Kyn/Trp) was raised, suggesting a higher IDO activity than in healthy people. Patients with higher Kyn/Trp ratios showed lower survival. IDO activity was also detected in AML cells after exposure to IFN-gammain vitro, suggesting that the higher Kyn/Trp ratio in serum of AML patients might have resulted from stimulated leukemic blast cells. Thus, in AML, the activity of IDO can be easily monitored, providing a tool for future clinical testing of IDO-blocking drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blast Crisis / pathology
  • Chromatography, High Pressure Liquid / methods
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
  • Interferon-gamma / pharmacology*
  • Kynurenine / blood
  • Leukemia, Myeloid, Acute / blood
  • Leukemia, Myeloid, Acute / enzymology*
  • Leukemia, Myeloid, Acute / mortality
  • Lymphocyte Activation
  • Survival Rate
  • Transcriptional Activation / drug effects*
  • Tryptophan / blood
  • Tumor Cells, Cultured

Substances

  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Kynurenine
  • Interferon-gamma
  • Tryptophan