Amplification of mitochondrial DNA in acute myeloid leukaemia.
There is a long-standing interest in the possible role of mitochondria in malignancy. We sought to discover whether amplification of mitochondrial DNA (mtDNA) occurred in leukaemia, and found it was often remarkably amplified in the blast cells of acute myeloid leukaemia (AML). We used gene dosage experiments to quantify the amount of mtDNA relative to nuclear DNA. DNA extracted from peripheral blood leucocytes or bone marrow of healthy individuals or patients was simultaneously hybridized with a probe for the mitochondrial genome and a control probe for the renin gene on human chromosome 1. Comparative densitometric ratios of approximately 1 were obtained between the two signals in 20 normal control peripheral blood samples. In contrast, comparative ratios in the range of 2-50 were observed in 25 AML samples and 13 of these showed 8-fold or greater amplification of mtDNA relative to normal peripheral blood controls. An additional four cases 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 remission. 18 cases of chronic granulocytic leukaemia (CGL) were also studied in chronic phase and showed mtDNA dosage levels equivalent to normal peripheral blood controls. However, 8/9 CGL patients showed mtDNA amplification during transformation from chronic phase. We conclude that amplification of mtDNA is an invariable feature of acute myeloid leukaemia and that it may be a useful marker for detecting transformation of CGL.
Boultwood
J
J
Department of Haematology, John Radcliffe Hospital, Oxford, U.K.
Fidler
C
C
Mills
K I
KI
Frodsham
P M
PM
Kusec
R
R
Gaiger
A
A
Gale
R E
RE
Linch
D C
DC
Littlewood
T J
TJ
Moss
P A
PA
Wainscoat
J S
JS
D000208:Acute Disease; D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm; D005784:Gene Amplification; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000175:diagnosis
D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm