Indoleamine 2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan 2,3-dioxygenase (TDO) represent some of the key immune regulators. Their increased activity has been demonstrated in a number of human malignancies but not yet in chronic myeloid leukemia (CML). In the present study, the activity of these enzymes was tested in 29 CML patients and 28 healthy subjects by monitoring the kynurenine (KYN)/tryptophan ratio. Serum samples taken prior to the therapy displayed a highly significant difference in KYN levels between the patient and control groups. However, increased KYN levels were detected in only 13 (44.8%) of these CML patients. The KYN levels in pretreatment sera of the patients correlated with the tumor burden. There was also a strong correlation between KYN levels and uric acid levels (UA). This suggests but does not prove the possible involvement of UA in activating IDO family of enzymes. Whenever tested, the increased KYN levels normalized in the course of the therapy. Patients with normal KYN levels in their pretreatment sera and subsequently treated with interferon-α, showed a transitory increase in their KYN levels. The present data indicate that CML should be added to the malignancies with an increased activity of the IDO family of enzymes and suggest that IDO inhibitors may be used in the treatment of CML patients.
Keywords: 3-dioxygenase; CML, chronic myeloid leukemia; IDO, indoleamine 2, 3-dioxygenase; INFα, interferon- α; INFγ, interferon-γ; KTI, kynurenine/tryptophan index; KYN, kynurenine; NK, natural killer; PBMC, peripheral blood mononuclear cells; Ph+, Philadelphia chromosome positive; T regs, regulatory T cells; TDO, tryptophan 2, 3-dioxygenase; TKI, tyrosine-kinase inhibitors; TRY, tryptophan; UA, uric acid.; chronic myeloid leukemia; indoleamine 2; kynurenine; tryptophan metabolism; uric acid.