Haema 2016; 7(3): 339-349
by Argiris S. Simeonidis
Hematology Division, Dept of Int. Medicine University of Patras, Medical School, Patras, Greece
With the term “sideroblastic anemia” several types of congenital or acquired anemias, characterized by the presence of cytoplasmic, perinuclear iron granules in bone marrow erythroblasts are described. Congenital sideroblastic anemia emerges as a result of point mutations in genes of the porphyrin biosynthetic pathway enzymes, whereas acquired sideroblastic anemia is a clonal hematopoietic stem-cell disorder, classified among the myelodysplatic syndromes. Acquired sideroblastic anemia originates from structural spliceosomal proteins, mainly of SF3B1, creating deficiency of the mitochondrial iron transporter ABCB7, which induces intramitochondrial iron accumulation and results in impairment of the mitochondrial function and induction of erythrpoblastic apoptosis. These patients usually exhibit elevated GDF-15 serum levels, as well as increased intracellular levels of mitochondrial ferritin and of Reactive Oxygen Species (ROS). Increased ROS levels inhibit several crucial tumor suppressor proteins, such as the cell cycle checkpoint inhibitors p15 and p27, and induce somatic DNA mutations and various other defects, thus favoring disease progression to a more aggressive MDS subtype or to acute leukemia. Such an evolution however, is less common in acquired sideroblastic anemia, as compared to other types of MDS. Acquired sideroblastic anemia may also be drug-induced, and in such cases it is completely reversible, following drug discontinuation. Some forms of congenital sideroblastic anemia respond favorably to pharmacological doses of pyridoxine, whereas rh-erythropoietin, with or without G-CSF may improve anemia, reducing the degree of ineffective erythropoiesis. Newer promising agents, such as activing receptor II ligand traps are still on clinical trials.