Sj. Hatfill et al., A ROLE FOR MITOCHONDRIAL-DNA IN THE PATHOGENESIS OF RADIATION-INDUCEDMYELODYSPLASIA AND SECONDARY LEUKEMIA, Leukemia research, 17(11), 1993, pp. 907-913
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.