Indoleamine 2,3-dioxygenase activity of acute myeloid leukemia cells can be measured from patients' sera by HPLC and is inducible by IFN-gamma.
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.
Corm
Selim
S
INSERM, unité 837, Equipe 3, Institut de Recherche sur le Cancer de Lille, Lille, France.
Berthon
Céline
C
Imbenotte
Michel
M
Biggio
Valeria
V
Lhermitte
Michel
M
Dupont
Caroline
C
Briche
Isabelle
I
Quesnel
Bruno
B
D001752:Blast Crisis / Q000473:pathology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D007737:Kynurenine / Q000097:blood; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000201:enzymology* / Q000401:mortality; D008213:Lymphocyte Activation; D015996:Survival Rate; D015533:Transcriptional Activation / Q000187:drug effects*; D014364:Tryptophan / Q000097:blood; D014407:Tumor Cells, Cultured
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D007371:Interferon-gamma; D014364:Tryptophan