Enhanced Renewal of Erythroid Progenitors in Myelodysplastic Anemia by Peripheral Serotonin.
SSRI
Tph1
anemia
erythropoiesis
myelodysplastic syndrome
serotonin
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
19 03 2019
19 03 2019
Historique:
received:
18
04
2018
revised:
30
12
2018
accepted:
20
02
2019
entrez:
21
3
2019
pubmed:
21
3
2019
medline:
30
4
2020
Statut:
ppublish
Résumé
Tryptophan as the precursor of several active compounds, including kynurenine and serotonin, is critical for numerous important metabolic functions. Enhanced tryptophan metabolism toward the kynurenine pathway has been associated with myelodysplastic syndromes (MDSs), which are preleukemic clonal diseases characterized by dysplastic bone marrow and cytopenias. Here, we reveal a fundamental role for tryptophan metabolized along the serotonin pathway in normal erythropoiesis and in the physiopathology of MDS-related anemia. We identify, both in human and murine erythroid progenitors, a functional cell-autonomous serotonergic network with pro-survival and proliferative functions. In vivo studies demonstrate that pharmacological increase of serotonin levels using fluoxetine, a common antidepressant, has the potential to become an important therapeutic strategy in low-risk MDS anemia refractory to erythropoietin.
Identifiants
pubmed: 30893598
pii: S2211-1247(19)30250-5
doi: 10.1016/j.celrep.2019.02.071
pii:
doi:
Substances chimiques
Serotonin
333DO1RDJY
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3246-3256.e4Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.