Kynurenine and uric acid levels in chronic myeloid leukemia patients

Abstract

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.

Predictive and prognostic role of serum neopterin and tryptophan breakdown in prostate cancer

“…In addition, the kynurenine pathway cannot be considered as a novel serum biomarker for detecting PCa. These findings are in accordance with other results showing that tryptophan, kynurenine, and KTR levels were not statistically different in patients with diagnosed PCa compared to the control group, in contrast to other cancer entities …”

“…(29) In leukemia patients, the IDO activity correlated with the tumor burden in the course of therapy. (30) This data supports the view that a higher degree of IDO expression plays a crucial role in tumor progression and worse survival. (31) Significant serum neopterin increase depends on the primary localization and the type of tumor, and mostly correlates with advanced tumor disease.…”

“…Lower tryptophan levels were closely related to rapid disease progression and shorter survival in melanoma patients . In leukemia patients, the IDO activity correlated with the tumor burden in the course of therapy . This data supports the view that a higher degree of IDO expression plays a crucial role in tumor progression and worse survival …”

“…These findings are in accordance with other results showing that tryptophan, kynurenine, and KTR levels were not statistically different in patients with diagnosed PCa compared to the control group, (41) in contrast to other cancer entities. (9,(29)(30)(31) Increased serum neopterin levels were reported to relate to advanced tumor stage. (42) However, our results did not support this theory as to whether preoperative neopterin or tryptophan degradation concentrations correlated with histopathological aspects in RP specimens.…”

Immunology of chronic myeloid leukemia: current concepts and future goals

“…Into that study 24 CML patients, enrolled prior to the start of any therapy, were included as well as the same number of age and sexmatched healthy control subjects. TABLE 1 summarizes the most important results [50,51]. In that study we tested also the presence of antibodies to several herpes viruses (HV) and HPV to find out whether the immunosuppressive effects of CML are reflected by the activation of these viruses which induce latent or persistent infections.…”