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Enhanced Renewal of Erythroid Progenitors in Myelodysplastic Anemia by Peripheral Serotonin.

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Sibon, David; Coman, Tereza; Rossignol, Julien; Lamarque, Mathilde; Kosmider, Olivier; Bayard, Elisa; Fouquet, Guillemette; Rignault, Rachel; Topçu, Selin; Bonneau, Pierre; Bernex, Florence; Dussiot, Michael; Deroy, Kathy; Laurent, Laetitia; Callebert, Jacques; Launay, Jean-Marie; Georgin-Lavialle, Sophie; Courtois, Geniviève; Côté, Francine (2019). Enhanced Renewal of Erythroid Progenitors in Myelodysplastic Anemia by Peripheral Serotonin. Cell Reports , vol. 26 , nº 12. p. 3246-3256. DOI: 10.1016/j.celrep.2019.02.071.

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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.

Type de document: Article
Mots-clés libres: SSRI; Tph1; anemia; erythropoiesis; myelodysplastic syndrome; serotonin
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 11 janv. 2020 15:45
Dernière modification: 11 janv. 2020 15:46
URI: http://espace.inrs.ca/id/eprint/8214

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