Metabolites of tryptophan catabolism are elevated in sera of patients with myelodysplastic syndromes and inhibit hematopoietic progenitor amplification

被引：28

作者：

Berthon, Celine ^{[1
,2
,3
]}

Fontenay, Michaela ^{[4
]}

Corm, Selim ^{[1
]}

Briche, Isabelle ^{[1
]}

Allorge, Delphine ^{[5
]}

Hennart, Benjamin ^{[5
]}

Lhermitte, Michel ^{[2
,5
]}

Quesnel, Bruno ^{[1
,2
,3
]}

机构：

[1] Inst Rech Canc Lille, INSERM, U837, Lille, France

[2] Univ Nord France, Lille, France

[3] CHU Lille, Serv Malad Sang, F-59037 Lille, France

[4] Hop Cochin, AP HP, Serv Hematol Biol, F-75674 Paris, France

[5] CHU Lille, Toxicol Lab, F-59037 Lille, France

来源：

LEUKEMIA RESEARCH | 2013年 / 37卷 / 05期

关键词：

IDO; Myelodysplastic syndrome; Kynurenine; Tryptophan; Hematopoiesis; ACUTE MYELOID-LEUKEMIA; PLASMACYTOID DENDRITIC CELLS; TUMORAL IMMUNE RESISTANCE; T-CELL; INDOLEAMINE 2,3-DIOXYGENASE; 3-HYDROXYANTHRANILIC ACID; EXPERIMENTAL ASTHMA; ANTHRANILIC ACID; PROLIFERATION; SUPPRESSION;

D O I：

10.1016/j.leukres.2013.02.001

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：573 / 579

页数：7

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