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Abstract

Cytogenetic and DNA studies were performed in 32 cases of
myeloma. In 30 patients, cytogenetic studies were carried out on both
stimulated and unstimulated peripheral blood cultures. In the other
two patients, cytogenetic studies were possible only on direct marrow
preparations. In eight of the patients, cytogenetic studies were )
performed on direct marrow preparations as well as peripheral blood
cultures, and in four of these there were parallel studies on direct
marrow preparations with added PHA.
In the unstimulated peripheral blood preparations, mitoses were
observed in 13 cultures from 12 cases, providing presumptive evidence
for the presence of abnormal cells in the peripheral blood of these
patients. In 19 stimulated cultures from 17 cases, abnormal mitoses
were present, seven of these involving a chromosome of Group 13-15. In
five cases a very large acrocentric chromosome was observed similar to
that previously described in some cases of myeloma. The 10 direct
marrow preparations were unsatisfactory by reason of the poor quality
of the chromosome preparations, and no improvement was found in
preparations with added PHA. Examination of peripheral blood cells
was found to be the more rewarding method. Significant aneuploidy was
not a feature of the chromosome studies. The results have been discussed,
particularly with reference to technical factors influencing the
frequency of demonstrable chromosomal abnormalities, and the relative
merits Of peripheral blood and bone marrow.
DNA studies were performed on marrow and peripheral blood from
24 patients. Twenty-two patients had DNA estimations on peripheral
blood mononuclear cells and 22 had DNA estimations performed on
marrow cells. Twenty patients had DNA studies on both peripheral blood
and marrow cells. These studies were performed because of the technical
difficulties found using standard cytogenetic techniques and the
inability of these methods to detect abnormalities in more than a
small proportion of all the cells present. The DNA studies revealed that
12 patients had a broad scatter of DNA values about the primary mode
in peripheral blood nucleated cells and an additional three patients
had a broad scatter about the primary mode in marrow cells. Three patients
had significant numbers of cells in marrow with marked hypodiploidy.
One patient in the terminal stages of the disease had a major mode
in the tetraploid range, and other modes at the diploid and octoploid
levels. Possible explanations for these patterns are discussed
including mechanisms for their production, the evidence for aneuploidy
in the myeloma cell and the limitations of the method.
The evidence for the presence of abnormal cells in the peripheral
blood in each case of myeloma was considered in the light of the results
of cytogenetic studies, DNA values and Romanowsky-stained buffy-coat
preparations. It was found that chromosomal abnormalities occur
frequently enaagh to provide useful information in the diagnosis of
difficult cases.
An attempt was made to correlate the chromosomal abnormalities
and the DNA values with the other features of the disease, in
particular the protein changes, since these represent a metabolic
aberration of the malignant cell. It was found that in this series of
patients no such correlation exists. Furthermore, there was no
association between the cytogenetic abnormalities and stage of the
disease, clinical state of the patient, the presence of hypermalcaemia
or any previous treatment the patient had received.

Item Type:	Thesis - MD
Authors/Creators:	Mundy, Gregory Robert
Keywords:	Bone marrow, Myeloma proteins, DNA
Copyright Holders:	The Author
Copyright Information:	Copyright 1972 the author - The University is continuing to endeavour to trace the copyright owner(s) and in the meantime this item has been reproduced here in good faith. We would be pleased to hear from the copyright owner(s).
Additional Information:	Thesis (M.D.)--University of Tasmania, 1973. References: l. 289-309
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