A role for mitochondrial DNA in the pathogenesis of radiation-induced myelodysplasia and secondary leukemia.

The onset of acute myeloid leukemia following ionizing radiation or alkylating agent exposure is antedated months to years by the development of 'preleukemia', or secondary myelodysplastic syndrome (sMDS). Mitochondrial abnormalities induced by chloramphenicol and clonal deletions of mitochondrial DNA (mt DNA) in the bone marrow create hematological 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 evidence to support this concept and suggest a role for select protease inhibitors in the clinical management of this disorder.