Diamond-Blackfan anemia (DBA), an inherited form of bone marrow failure, and myelodysplastic syndrome arising from a deletion of a portion of chromosome 5 [del(5q) MDS], an acquired disease, are both characterized by anemia, or insufficient levels of red blood cells. As these cells carry oxygen from the lungs to all of the body’s organs and tissues, deficient numbers of red blood cells can cause a wide range of serious medical issues. A new study, based on experiments in an animal model and with cultured human cells, suggests that the anemia associated with these disorders can be alleviated with an amino acid supplement.
Previous studies have indicated that DBA and del(5q) MDS are caused by an insufficient level of one or more of the protein components of ribosomes. Ribosomes are complex structures of proteins and ribonucleic acids that perform the final step of translating the DNA “blueprint” into proteins that carry out the functions of cells and tissues. Mutations in nine genes that encode ribosomal proteins have been identified in patients with DBA, accounting for about half of the diagnosed cases.
In the current study, researchers modeled DBA and del(5q) MDS in zebrafish using a targeted approach to reduce the levels of two specific ribosomal proteins that have been implicated in these diseases. They observed that, as in humans, diminished levels of these proteins in zebrafish resulted in severe anemia. When the animals were treated with leucine, there was a significant improvement in the animals’ anemia. Similar results were seen in experiments with cultured human blood cells. Leucine is an “essential” amino acid that must be part of the diet because it cannot be synthesized in animals and humans. Leucine has previously been shown to enhance ribosome function in cells, potentially by activating a biologic pathway (known as the mTOR pathway) that integrates multiple signals inside the cell and plays a role in protein synthesis. In this study, the researchers showed that leucine activates this pathway in blood cells, a result that may explain how leucine improved anemia in the zebrafish.
The only true cure for DBA is a bone marrow transplant, which is a very limited treatment approach because suitable bone marrow donors are rarely available and serious risks are associated with the procedure. The novel findings described in this study show that simple nutritional supplementation may reverse many of the manifestations of DBA and del(5q) MDS and provide a rationale for future studies that will explore the potential effectiveness and safety of nutritional leucine supplements to treat patients with these rare disorders.
Payne EM, Virgilio M, Narla A, et al. L-leucine improves the anemia and developmental defects associated with Diamond-Blackfan anemia and del(5q) MDS by activating the mTOR pathway. Blood 120: 2214-2224, 2012.