High serum concentration of L-kynurenine predicts unfavorable outcomes in patients with acute myeloid leukemia

Abstract

The immunomodulatory effects of indoleamine 2,3-dioxygenase (IDO) are ascribed to its ability to catalyze the breakdown of the L-tryptophan along the L-kynurenine pathway. Because blasts from patients with acute myeloid leukemia (AML) express IDO, the goal of this study was to investigate the role of L-kynurenine as a prognostic marker for AML. We enrolled 48 AML patients. L-kynurenine concentrations were measured by high-performance liquid chromatography. The median serum L-kynurenine level was 1.67 μM. There was no significant difference in the complete remission rate between patients with L-kynurenine < 2.4 (77%) and ≥ 2.4 μM (75%). However, 3-year overall survival (OS) rates were significantly better in patients with low L-kynurenine levels (76%) than in those with high L-kynurenine levels (11%) (p < 0.0001). Furthermore, in intermediate-risk cytogenetics patients, only L-kynurenine was significantly associated with OS (p < 0.005). Multivariate analyses revealed that L-kynurenine and high leukocyte count were independent prognostic factors.

Keywords::

• L-kynurenine
• immunological tolerance
• indoleamine 2,3-dioxygenase
• prognostic factor
• L-tryptophan catabolism
• acute myeloid leukemia (AML)

Acknowledgements

This study was conducted in cooperation with the Gifu Hematology Study Group. We thank the participating physicians (Drs Takeshi Takahashi, Michio Sawada, Toshiki Yamada, Kenji Fukuno, Hideko Goto, Senji Kasahara, Takeshi Yoshikawa, Soranobu Ninomiya, and Eri Takada) for providing bone marrow samples from the patients. We also thank Ms Chiyoko Sano, Ms Hitomi Fujisawa, Ms Sakiko Sumi and Ms Eriko Kunishima for secretarial and technical assistance.

Potential conflict of interest

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