Glucocorticoids improve erythroid progenitor maintenance and dampen Trp53 response in a mouse model of Diamond-Blackfan anaemia.

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.

• Author: Sara Sjögren; Kavitha Siva; Shamit Soneji; Amee J George; Marcus Winkler; Pekka Jaako; Marcin Wlodarski; Stefan Karlsson; Ross D Hannan; Johan Flygare
• Department/s: Stem Cells to Red Blood Cells; Division of Molecular Medicine and Gene Therapy; Division of Molecular Hematology (DMH); BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation; StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
• Publishing year: 2015
• Language: English
• Pages: 517-529
• Publication/Series: British Journal of Haematology
• Volume: 171
• Issue: 4
• Full text: - 4 kB; Download statistics
• Links: http://www.ncbi.nlm.nih.gov/pubmed/26305041?dopt=Abstract; http://dx.doi.org/10.1111/bjh.13632
• Document type: Journal article
• Publisher: Wiley-Blackwell
• Topic: Hematology
• Status: Published
• Research group: Stem Cells to Red Blood Cells
• ISBN/ISSN/Other: ISSN: 0007-1048