Glucocorticoids improve erythroid progenitor maintenance and dampen Trp53 response in a mouse model of Diamond-Blackfan anaemia
Sara E Sjogren, Kavitha Siva, Shamit Soneji, Amee J George, Marcus Winkler, Pekka Jaako, Marcin Wlodarski, Stefan Karlsson, Ross D Hannan, Johan Flygare
British Journal of Haematology | WILEY | Published : 2015
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 DB..View full abstract
We thank the staff of the BMC animal facility for excellent animal care and Abdul Ghani Alattar for cDNA preparations. We also thank Carolina Guibentif and Alexander Mattebo for critical revision of this manuscript. We would also like to acknowledge the Australian Diamond Blackfan Anaemia (ADBA) programme members, consisting of Sheren Al-Obaidi, Sarah CE Bray, Richard J D'Andrea, Jianmin Ding, Amee J George, Thomas J Gonda, S Peter Klinken, Piyush Madhamshettiwar, Lorena Nunez Villacis, Richard B Pearson, Ben Saxon, Hamish S Scott, Kaylene J Simpson, Adam Stephenson, Amilia Wee, Louise N Winteringham, Mei S Wong, and Ross D Hannan for their contribution to this work. This work was supported by the Soderberg Foundation, The Diamond-Blackfan Anemia Foundation, DBA Canada, Swedish Research Council, Ellen Bacharach's Foundation, Ake Wiberg's Foundation, Marie Curie Integration Grant and an Australian Diamond Blackfan Anaemia (ADBA) programme grant from the Captain Courageous Foundation (www.captaincourageousfoundation.com).