Dietary L-leucine improves the anemia in a mouse model for Diamond-Blackfan anemia
Dietary L-leucine improves the anemia in a mouse model for Diamond-Blackfan anemia
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DOI：
10.1182/blood-2012-05-431437
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发表时间：
2012-09-13
期刊：
影响因子：
20.3
通讯作者：
Karlsson, Stefan
中科院分区：
文献类型：
--
作者：
Jaako, Pekka;Debnath, Shubhranshu;Karlsson, Stefan
Diamond-Blackfan贫血（DBA）是一种先天性红细胞发育不全，由核糖体蛋白编码基因的功能性单倍不足引起。最近，一项病例研究报告了一名患者，该患者在接受氨基酸L-亮氨酸治疗后变得不依赖输血。因此，我们已经使用我们最近生成的RPS 19缺陷型DBA小鼠模型验证了L-亮氨酸的治疗效果。L-亮氨酸的给药显著改善了Rps 19缺陷小鼠的贫血（血红蛋白浓度改善19%;红细胞数量增加18%），增加了骨髓细胞构成，并减轻了应激性造血。此外，对L-亮氨酸的治疗反应似乎对Rps 19缺陷型造血具有特异性，并且与p53活性的下调相关。我们的研究支持L-亮氨酸作为DBA治疗剂的临床试验的基本原理。（血。2012;120（11）：2225-2228）
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. (Blood. 2012;120(11):2225-2228)