Fetal hemoglobin rescues ineffective erythropoiesis in sickle cell disease
| Autor: | Sara El Hoss, Sylvie Cochet, Auria Godard, Hongxia Yan, Michaël Dussiot, Giacomo Frati, Bénédicte Boutonnat-Faucher, Sandrine Laurance, Olivier Renaud, Laure Joseph, Annarita Miccio, Valentine Brousse, Mohandas Narla, Wassim El Nemer |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Haematologica, Vol 106, Iss 10 (2020) |
| Druh dokumentu: | article |
| ISSN: | 0390-6078 1592-8721 |
| DOI: | 10.3324/haematol.2020.265462 |
| Popis: | While ineffective erythropoiesis has long been recognized as a key contributor to anemia in thalassemia, its role in anemia of sickle cell disease (SCD) has not been critically explored. Using in vitro and in vivo derived human erythroblasts we assessed the extent of ineffective erythropoiesis in SCD. Modeling the bone marrow hypoxic environment, we found that hypoxia induces death of sickle erythroblasts starting at the polychromatic stage, positively selecting cells with high levels of fetal hemoglobin (HbF). Cell death was associated with cytoplasmic sequestration of heat shock protein 70 and was rescued by induction of HbF synthesis. Importantly, we document that in the bone marrow of SCD patients similar cell loss occurs during the final stages of terminal differentiation. Our study provides evidence for ineffective erythropoiesis in SCD and highlights an anti-apoptotic role for HbF during the terminal stages of erythroid differentiation. These findings imply that the beneficial effect on anemia of increased HbF levels is not only due to the increased life span of red cells but also a consequence of decreased ineffective erythropoiesis. |
| Databáze: | Directory of Open Access Journals |
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