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.

• Author: Pekka Jaako; Shubhranshu Debnath; Karin Olsson; David Bryder; Johan Flygare; Stefan Karlsson
• Department/s: Division of Molecular Medicine and Gene Therapy; Department of Experimental Medical Science; Hematopoiesis and Gene Therapy; StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
• Publishing year: 2012
• Language: English
• Pages: 2225-2228
• Publication/Series: Blood
• Volume: 120
• Issue: 11
• Links: http://www.ncbi.nlm.nih.gov/pubmed/22791294?dopt=Abstract; http://dx.doi.org/10.1182/blood-2012-05-431437
• Document type: Journal article
• Publisher: American Society of Hematology
• Topic: Hematology
• Status: Published
• Research group: Hematopoiesis and Gene Therapy
• ISBN/ISSN/Other: ISSN: 1528-0020