Biology of sideroblastic anemia

Sideroblastic anemia is characterized by anemia with ring sideroblasts produced by the bone marrow. Sideroblasts are formed by disutilization and deposit of iron in the mitochondoria. There are two forms of sideroblastic anemia: congenital and acquired. Congenital sideroblastic anemia is caused by mutations in genes involved in heme biosynthesis, iron-sulfur (Fe-S) cluster biogenesis, or mitochondrial metabolism. Although there is a variation in the mutated genes among races, the most common congenital sideroblastic anemia is X-linked sideroblastic anemia caused by mutations in the erythroid-specific δ-aminolevulinate synthase gene, which is the first enzyme of heme biosynthesis in erythroid cells. The most commonly acquired sideroblastic anemia is myelodysplastic syndrome with ring sideroblasts (MDS-RS). It has been shown that the splicing factor 3b subunit 1 (SF3B1) gene, which is a core component of the RNA splicing complex, is highly mutated in MDS-RS, although the underlying mechanism of the onset of the disease by the mutation of the SF3B1 gene remains unclear. Molecular analysis will contribute to the development of effective treatment for congenital and acquired sideroblastic anemia, which are intractable diseases.