Portal de Periódicos da CAPES

Enhanced Renewal of Erythroid Progenitors in Myelodysplastic Anemia by Peripheral Serotonin

2019; Cell Press; Volume: 26; Issue: 12 Linguagem: Inglês

10.1016/j.celrep.2019.02.071

2639-1856

David Sibon, Téreza Coman, Julien Rossignol, Mathilde Lamarque, Olivier Kosmider, Elisa Bayard, Guillemette Fouquet, Rachel Rignault, Selin Topçu, Pierre Bonneau, Florence Bernex, Michaël Dussiot, Kathy Deroy, Lætitia Laurent, Jacques Callebert, Jean‐Marie Launay, Sophie Georgin‐Lavialle, G. Courtois, Luc Maroteaux, Cathy Vaillancourt, Michaëla Fontenay, Olivier Hermine, Francine Côté,

Acute Lymphoblastic Leukemia research

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.