A HETEROPLASMIC POINT MUTATION OF MITOCHONDRIAL TRNA(LEU)(CUN) IN NONLYMPHOID HEMATOPOIETIC-CELL LINEAGES FROM A PATIENT WITH ACQUIRED IDIOPATHIC SIDEROBLASTIC ANEMIA

Acquired idiopathic sideroblastic anaemia (AISA) has been proposed to be a disorder of mitochondrial DNA (mtDNA). The hallmark of mitochondr ial iron overload may be attributable to a respiratory chain defect le ading to impaired reduction of ferric iron (Fe3+) to ferrous iron (Fe2 +), which is essential to the last step of mitochondrial haem biosynth esis. In a 71-year-old patient we identified a point mutation in one o f the two mitochondrial transfer-RNAs coding for leucine (tRNA(leu(CUN ))). The mutation involves a G --> A transition in the anticodon loop, immediately adjacent to the anticodon triplet (mtDNA position 12301). The mutated guanine is highly conserved in a wide range of species. T he mutation is heteroplasmic, i.e. there is a mixture of normal and mu tated mitochondrial genomes (ratio c. 50:50). Heteroplasmy of mtDNA is not found in normal individuals, but is a typical feature of mitochon drial cytopathies. The point mutation was present in the patient's bon e marrow and whole blood samples, in purified platelets, and in the gr anulocyte/erythrocyte pellet after mononuclear cell separation by dens ity gradient centrifugation. The mutation was not found in T- and B-ly mphocytes isolated by immunomagnetic bead separation. It was also abse nt from buccal mucosa cells and cultured skin fibroblasts. This patter n of involvement suggests that the mutation occurred in a self-renewin g myeloid stem cell of the CFU-GEMM type.