Genetic rearrangements in leukaemia and lymphoma / J.M. Goldman, D.G. Harnden.

Date:
1986
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Genetic rearrangements in leukaemia and lymphoma / J.M. Goldman, D.G. Harnden. Source: Wellcome Collection.

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    GENETIC REARRANGEMENTS IN LEUKAEMIA AND LYMPHOMA 19 randomly occurring genetic changes or are there regions of the chromosomes where such modifications are more likely to occur? If the observed aberrations are derived by selection, we have a range of clastogens which could be leukaemogens. If the changes are induced specifically, is there a particular agent which can modify the chromosome in a particular and repeatable way? Or is it possibly a reflection of some functional association between chromosome regions? In the early 1960's there was a lot of interest in viruses as a cause of human leukaemia but there was remarkably little evidence, in spite of what was by that time the overwhelming evidence of virus involvement in murine and avian leukaemia. One particular observation made at this time linked in my mind genetic change in leukaemia and the potential of viruses as agents of specific genetic change - a patient with Klinefelter's syndrome who was a 46XX/47,XXY mosaic, also had chronic myeloid leukaemia^ ' and there were both normal cells and Ph' positive cells in both cell lines. The most probable explanation was that the Ph^ chromosome had arisen on two separate occasions, in the same individual. One can, therefore, postulate a directed exchange rather than the improbable occurrence by chance of two identical genetic lesions in the same individual. At that time it seemed to me that the involvement of a virus in this process would be one way to explain this phenomenon. This led me to become involved in the study of viruses as specific chromosome breaking agents^^ and so to the study of cellular transformation by oncogenic viruses. Cellular transformation by viruses The phenomenon of cellular transformation by oncogenic viruses depends, in most instances, on the delivery of a specific region of the virus genome to the cell which may be integrated into the host cell genome (adenovirus, polyoma virus), or is enabled to persist in a free replicating episomal form (EB virus, papilloma viruses). The cell acquires new properties, which resemble in many respects those of malignant cells, but the behaviour of these cells in vivo will depend upon the precise cell-virus interaction and upon the response of the host to the transformed cell - for example, not all virus transformed cells are malignant. Studies with both DNA virus and RNA virus have shown that the transforming activity usually resides in a small and clearly defined region of the virus genome. Two recent reviews of polyoma virus as a model for a DNA virus^^ and avian retrovirus as a model for RNA viruses^ give up-to-date summaries. So far as leukaemia and lymphoma are concerned, the only viruses known to be directly involved are the RNA retroviruses and members of the DNA herpesvirus group. The mechanism by which the heфes viruses interact with cells is poorly understood partly, at least, because of the large complex genome and partly because of the absence of a suitable in vitro model system. The involvement of EB virus in the aetiology of Burkitt's tumour is well documented; but, as yet, the regions of the genome which are involved in cellular transformation are not clearly defined.