AMPLIFICATION OF MITOCHONDRIAL-DNA IN ACUTE MYELOID-LEUKEMIA

There is a long-standing interest in the possible role of mitochondria in malignancy. We sought to discover whether amplification of mitocho ndrial DNA (mtDNA) occurred in leukaemia, and found it was often remar kably amplified in the blast cells of acute myeloid leukaemia (AML). W e used gene dosage experiments to quantify the amount of mtDNA relativ e to nuclear DNA. DNA extracted from peripheral blood leucocytes or bo ne marrow of healthy individuals or patients was simultaneously hybrid ized with a probe for the mitochondrial genome and a control probe for the renin gene on human chromosome 1. Comparative densitometric ratio s of approximately 1 were obtained between the two signals in 20 norma l control peripheral blood samples. In contrast, comparative ratios in the range of 2-50 were observed in 25 AML samples and 13 of these sho wed 8-fold or greater amplification of mtDNA relative to normal periph eral blood controls. An additional four eases of AML were investigated at both presentation and remission and showed 3-10-fold amplification of mtDNA at presentation, but no amplification when in clinical remis sion. 18 cases of chronic granulocytic leukaemia (CGL) were also studi ed in chronic phase and showed mtDNA dosage levels equivalent to norma l peripheral blood controls. However, 8/9 CGL patients showed mtDNA am plification during transformation from chronic phase. We conclude that amplification of mtDNA is an invariable feature of acute myeloid leuk aemia and that it may be a useful marker for detecting transformation of CGL.