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Article Dans Une Revue Cell Reports Année : 2019

Enhanced Renewal of Erythroid Progenitors in Myelodysplastic Anemia by Peripheral Serotonin

Olivier Kosmider
Michaela Fontenay

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.
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Dates et versions

hal-02086600 , version 1 (01-04-2019)

Identifiants

Citer

David Sibon, Tereza Coman, Julien Rossignol, Mathilde Lamarque, Olivier Kosmider, et al.. Enhanced Renewal of Erythroid Progenitors in Myelodysplastic Anemia by Peripheral Serotonin. Cell Reports, 2019, 26 (12), pp.3246-3256.e4. ⟨10.1016/j.celrep.2019.02.071⟩. ⟨hal-02086600⟩
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