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Mitochondrial DNA heteroplasmy in radiation induced myelodysplasia and leukaemia
Author(s)
La Cock, Charles J. R.
Date Issued
1996
Type
Thesis
Publisher
Cape Technikon
Abstract
Haematological defects observed in clonal deletions of mtDNA and
the inhibition of mitochondrial function by benzene and
chloramphenicol, suggest a role for mtDNA in the pathogenesis of
radiation - induced preleukaemia (MDS). The fact that leukaemia
cells contain abnormal mitochondria and abnormally structured
mtDNA, makes it reasonable to assume mtDNA mutations could be
central to the pathogenesis of both MDS and leukaemia. It was
decided to examine MDS patients for the presence of mtDNA length
mutations (dimers and cocantameres). Such topological forms have
already been reported in the literature in association with human
leukaemia. These steric considerations suggest that mtDNA dimers
are probably non-functional due to supercoiling.
Thus, it was
felt that a progressive accumulation of non-functional dimers in
the haematopoietic compartment could account for many of the
clinical features associated with MDS. Transmission electron
microscopy was used to examine haematopoietic mtDNA in the bone
marrow of six patients with MDS. Abnormal mtDNA dimer formation
was found in all instances. The proportional number of these
dimers were found to roughly correlate with the Myeloid/
Erythroid cell ratio in the bone marrow, and it appeared likely
that the dimers were generated in the myeloid compartment during
early MDS.
the inhibition of mitochondrial function by benzene and
chloramphenicol, suggest a role for mtDNA in the pathogenesis of
radiation - induced preleukaemia (MDS). The fact that leukaemia
cells contain abnormal mitochondria and abnormally structured
mtDNA, makes it reasonable to assume mtDNA mutations could be
central to the pathogenesis of both MDS and leukaemia. It was
decided to examine MDS patients for the presence of mtDNA length
mutations (dimers and cocantameres). Such topological forms have
already been reported in the literature in association with human
leukaemia. These steric considerations suggest that mtDNA dimers
are probably non-functional due to supercoiling.
Thus, it was
felt that a progressive accumulation of non-functional dimers in
the haematopoietic compartment could account for many of the
clinical features associated with MDS. Transmission electron
microscopy was used to examine haematopoietic mtDNA in the bone
marrow of six patients with MDS. Abnormal mtDNA dimer formation
was found in all instances. The proportional number of these
dimers were found to roughly correlate with the Myeloid/
Erythroid cell ratio in the bone marrow, and it appeared likely
that the dimers were generated in the myeloid compartment during
early MDS.
Additional information
Thesis (MTech (Medical Technology))--Cape Technikon, 1996.
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187016100_La Cock_CJR_Mtech_Bio_Tech_HWSci_1996_99000786.pdf
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Thesis
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