A ROLE FOR MITOCHONDRIAL-DNA IN THE PATHOGENESIS OF RADIATION-INDUCEDMYELODYSPLASIA AND SECONDARY LEUKEMIA

The onset of acute myeloid leukemia following ionizing radiation or al kylating agent exposure is antedated months to years by the developmen t of 'preleukemia', or secondary myelodysplastic syndrome (sMDS). Mito chondrial abnormalities induced by chloramphenicol and clonal deletion s of mitochondrial DNA (mt DNA) in the bone marrow create hematologica l defects similar to sMDS, and abnormal dimers of mt DNA are observed in acute leukemia. This suggests a role for mt DNA in the pathogenesis of sMDS and secondary leukemia. We outline disparate experimental evi dence to support this concept and suggest a role for select protease i nhibitors in the clinical management of this disorder.