Cytogenetic studies and DNA content in Myeloma : with reference to other features of the disease

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.