Dietary L-leucine improves the anemia in a mouse model for Diamond-Blackfan anemia.

Summary, in English

Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes encoding for ribosomal proteins. Recently, a case study reported a patient who became transfusion-independent in response to treatment with the amino acid L-leucine. Therefore, we have validated the therapeutic effect of L-leucine using our recently generated mouse model for RPS19-deficient DBA. Administration of L-leucine significantly improved the anemia in Rps19-deficient mice (19 % improvement in hemoglobin concentration; 18% increase in the number of erythrocytes), increased the bone marrow cellularity and alleviated stress hematopoiesis. Furthermore, the therapeutic response to L-leucine appeared specific for Rps19-deficient hematopoiesis and was associated with downregulation of p53 activity. Our study supports the rationale for clinical trials of L-leucine as a therapeutic agent for DBA.

• Författare: Pekka Jaako; Shubhranshu Debnath; Karin Olsson; David Bryder; Johan Flygare; Stefan Karlsson
• Avdelning/ar: Avdelningen för molekylärmedicin och genterapi; Institutionen för experimentell medicinsk vetenskap; Hematopoes och genterapi; StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
• Publiceringsår: 2012
• Språk: Engelska
• Sidor: 2225-2228
• Publikation/Tidskrift/Serie: Blood
• Volym: 120
• Issue: 11
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/22791294?dopt=Abstract; http://dx.doi.org/10.1182/blood-2012-05-431437
• Dokumenttyp: Artikel i tidskrift
• Förlag: American Society of Hematology
• Ämne: Hematology
• Status: Published
• Forskningsgrupp: Hematopoiesis and Gene Therapy
• ISBN/ISSN/Övrigt: ISSN: 1528-0020