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

Leuk Lymphoma. 2016;57(1):92-8. doi: 10.3109/10428194.2015.1041388. Epub 2015 Jun 18.

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor*
  • Chromosome Banding
  • Female
  • Humans
  • Immunophenotyping
  • Kynurenine / blood*
  • Leukemia, Myeloid, Acute / blood*
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / mortality*
  • Male
  • Middle Aged
  • Prognosis
  • ROC Curve
  • Remission Induction
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Kynurenine