Two recent studies provide further preclinical evidence that L-leucine may play an important role in treating Diamond-Blackfan anemia (DBA), and consequently reduce transfusion dependence. DBA is a rare genetic bone marrow disorder characterized by macrocytic anemia and insufficient or absent erythroid precursors. It had previously been shown that approximately 25% of DBA patients had mutations in the ribosomal protein RPS19 gene, most of which resulted in RPS19 haploinsufficiency. Furthermore, a case study had demonstrated that L-leucine supplementation in a DBA patient led to improved erythropoiesis. In Blood, Dr. Pekka Jaako and colleagues from Lund University report that L-leucine supplementation significantly increased hemoglobin levels and the number of erythrocytes in RPS19-deficient mice. In addition, a study from Harvard Medical School led by Dr. Elspeth Payne suggests that L-leucine improved anemia in RPS19-deficient zebrafish embryos. Payne and colleagues further demonstrated that knockdown of RPS19 in human CD34+ cells resulted in decreased erythroid cells, but that erythroid cell differentiation increased after culture with L-leucine. L-leucine is thought to up-regulate ribosome biosynthesis through the mTOR pathway, although specific mechanisms are not entirely clear.
1. Payne EM, Virgilio M, Narla A, Sun H, Levine M, Paw BH, Berliner N, Look AT, Ebert BL, Khanna-Gupta A. L-leucine improves the anemia and developmental defects associated with Diamond-Blackfan anemia and del(5q) MDS by activating the mTOR pathway. Blood 2012;120: 2214-24.
2. Jaako P, Debnath S, Olsson K, Bryder D, Flygare J, Karlsson S. Dietary L-leucine improves the anemia in a mouse model for Diamond-Blackfan anemia. Blood 2012;120: 2225-8.
3. Kamimae-Lanning AN, Kurre P. L-leucine alleviates Diamond-Blackfan anemia. Blood 2012;120: 2157-8.