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.

    38/200 (page 22)
    22 GENETIC REARRANGEMENTS activation of a gene may only be important, if this occurs in a cell which is differentiated along a specific pathway. However, we must be very careful not to assume that in gross chromosomal terms the proximity of an one gene locus to a rearrangement breakpoint is a close association in both causal and molecular terms. To take an example outside the leukaemias - the deletion, at band lip 13, associated with the Wilms' tumour aniridia syndrome, does not include the locus of the c-Ha-ra52 gene which is known to be located on the short arm of chromosome ll^^'^^. In view of our work on ataxia-telangiectasia, it is tempting to speculate that there is an one gene at 14ql2 and that the exchange involving this locus also involves other chromosomal sites - the loci of genes which are activated in T cell differentiation. If this is correct, it is a further example of activation leading to only part of the neoplastic phenotype. Conclusions 1. Specific cellular genes are critical for the development of neoplasia. 2. Their modification is associated with leukaemia. 3. Modified genes may: (a) acquire modification in situ, or (b) be inserted by a virus. 4. Modification of these genes may be only one part of the neoplastic process. GENERAL CONSIDERATIONS It seems likely that any external influence which causes genomic rearrangement will predispose the patient to the development of leukaemia (or cancer). In the first place the changes that are induced may be random, but later selection occurs for specific rearrangements because of the very special nature of the alterations in cell behaviour that they bring about. The possibility that rearrangements occur in particular regions of the genome - either because of the specificity of an exogenous agent (such as a virus), or because of a functional relationship between such regions - cannot at present be excluded. Oncogenic viruses are probably a special case where a rearranged primed one gene is inserted direct into the genome. However, in other cases the chromosomal rearrangement is almost certainly involved in the inappropriate activation or alteration of the function of normal cellular genes controlling important cellular processes. While the understanding of the basic biology is important, there may also be long term implications for therapy. Any understanding of the function of the genes involved in these arrangements should enable specific therapies to be targeted at those particular processes. This gives the possibility of regulation of the leukaemic cell without necessarily destroying it. A final stage may involve the total breakdown in cell control of chromosomal structure and replication. Beyond that point only cell killing is likely to effect any control on the leukaemic process.