Glucocorticoids improve erythroid progenitor maintenance and dampen Trp53 response in a mouse model of Diamond-Blackfan anaemia.
Författare
Summary, in English
Diamond-Blackfan anaemia (DBA) is a rare congenital disease causing severe anaemia and progressive bone marrow failure. The majority of patients carry mutations in ribosomal proteins, which leads to depletion of erythroid progenitors in the bone marrow. As many as 40% of all DBA patients receive glucocorticoids to alleviate their anaemia. However, despite their use in DBA treatment for more than half a century, the therapeutic mechanisms of glucocorticoids remain largely unknown. Therefore we sought to study disease specific effects of glucocorticoid treatment using a ribosomal protein s19 (Rps19) deficient mouse model of DBA. This study determines for the first time that a mouse model of DBA can respond to glucocorticoid treatment, similar to DBA patients. Our results demonstrate that glucocorticoid treatment reduces apoptosis, rescues erythroid progenitor depletion and premature differentiation of erythroid cells. Furthermore, glucocorticoids prevent Trp53 activation in Rps19-deficient cells- in a disease-specific manner. Dissecting the therapeutic mechanisms behind glucocorticoid treatment of DBA provides indispensible insight into DBA pathogenesis. Identifying mechanisms important for DBA treatment also enables development of more disease-specific treatments of DBA.
Avdelning/ar
- Stamceller till röda blodkroppar
- Avdelningen för molekylärmedicin och genterapi
- Avdelningen för molekylär hematologi
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
Publiceringsår
2015
Språk
Engelska
Sidor
517-529
Publikation/Tidskrift/Serie
British Journal of Haematology
Volym
171
Issue
4
Fulltext
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Wiley-Blackwell
Ämne
- Hematology
Status
Published
Forskningsgrupp
- Stem Cells to Red Blood Cells
ISBN/ISSN/Övrigt
- ISSN: 0007-1048