Dietary L-leucine improves the anemia in a mouse model for Diamond-Blackfan anemia.
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 down-regulation of p53 activity. Our study supports the rationale for clinical trials of L-leucine as a therapeutic agent for DBA.
Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden.
Pekka
P
Jaako
Shubhranshu
S
Debnath
Karin
K
Olsson
David
D
Bryder
Johan
J
Flygare
Stefan
S
Karlsson
D029503:Anemia, Diamond-Blackfan / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D015536:Down-Regulation; D004906:Erythrocyte Count; D055785:Gene Knockdown Techniques; D006397:Hematinics / Q000627:therapeutic use*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006454:Hemoglobins / Q000032:analysis; D007930:Leucine / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D012269:Ribosomal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D006397:Hematinics; D006454:Hemoglobins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; C040343:ribosomal protein S19; D007930:Leucine