title: Metabolites of tryptophan catabolism are elevated in sera of patients with myelodysplastic syndromes and inhibit hematopoietic progenitor amplification.
abstract: 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.
authors: INSERM, unité 837, Institut pour la Recherche sur le Cancer de Lille, Lille, France.
authors: Céline
authors: C
authors: Berthon
authors: Michaela
authors: M
authors: Fontenay
authors: Selim
authors: S
authors: Corm
authors: Isabelle
authors: I
authors: Briche
authors: Delphine
authors: D
authors: Allorge
authors: Benjamin
authors: B
authors: Hennart
authors: Michel
authors: M
authors: Lhermitte
authors: Bruno
authors: B
authors: Quesnel
mesh_terms: D000328:Adult; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007737:Kynurenine / Q000097:blood*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000473:pathology; D014364:Tryptophan / Q000097:blood*; D014366:Tryptophan Oxygenase / Q000378:metabolism
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan; D014366:Tryptophan Oxygenase