John Libbey Eurotext



Molecular pathology of sideroblastic anemia Volume 9, issue 2, Mars 2003


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Division d‘hématologie, hôpital cantonal Universitaire, Genève, Suisse Division d‘hématologie, CHUV, Lausanne, Suisse

There are three types of sideroblastic anemia (SA): hereditary, primary acquired (which belongs to the myelodysplastic syndromes), and secondary to drugs and various toxic agents. A mutation of the ALAS2 gene is by far the most frequent cause of hereditary SA. To date, 28 different mutations have been described and their X‐linked transmission has led to interesting conclusions concerning X inactivation in certain women with late development of the disease. Sideroblastic anemia with ataxia has been shown to be secondary to mutations at the level of another X‐linked gene, the ABC7 gene which codes for a transporter to the mitochondrial membrane. Pearson‘s syndrome is an example of a primary mitochondrial pathology leading to, amongst other things, SA. Finally, in its autosomally transmitted form, only thiamine‐responsive megaloblastic anemia (TRMA) has been elucidated at the molecular level. Primary acquired sideroblastic anemia (PASA) may either affect erythrocytic cells only (excellent prognosis), or be characterized by a dysplasia affecting all cell lines (increased risk of leukemic transformation), or be associated with a thrombocytosis. At the molecular level, at least 18 different mutations have been described in mitochondrial DNA from hematopoietic tissue, while the mitochondrial DNA from buccal mucosa, or the fibroblastic DNA, was intact. Given the proliferative advantage of the sideroblastic clone, the demonstration of karyotypic anomalies in about 30% of cases, and the possible evolution to leukemia, the presence of other somatic mutations ‐‐ at the level of the hematopoietic stem cell influencing the proliferation, differentiation and maturation of hematopoietic precursors ‐‐ is strongly suspected. These mutations have yet to be determined. The mechanism of SA secondary to lead, zinc, chloramphenicol and certain tuberculostatic agents has been elucidated.