Leuk Res. 2013 May;37(5):573-9. doi: 10.1016/j.leukres.2013.02.001. Epub 2013 Feb 28.
Metabolites of tryptophan catabolism are elevated in sera of patients with myelodysplastic syndromes and inhibit hematopoietic progenitor amplification.
Berthon C, Fontenay M, Corm S, Briche I, Allorge D, Hennart B, Lhermitte M, Quesnel B.
INSERM, unité 837, Institut pour la Recherche sur le Cancer de Lille, Lille, France.
Tryptophan catabolism, which is mediated by the enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO), produces kynurenine. Kynurenine itself is converted by downstream enzymes into secondary catabolites. We evaluated the serum levels of primary and secondary tryptophan catabolites in a cohort of patients with myelodysplastic syndromes (MDS). The MDS patients showed significantly higher levels tryptophan catabolites which correlated with cytopenia. The tryptophan catabolites inhibited progenitor expansion during the in vitro culture of hematopoietic cells. Thus, MDS patients are characterized by high tryptophan catabolism resulting in elevated primary and secondary metabolites, which both have inhibitory effects on hematopoiesis. |
