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.

    21/200 (page 5)
    GENETIC REARRANGEMENTS IN LEUKAEMIA AND LYMPHOMA 5 frank neoplasia. A focal abnormality in the haematopoietic system would rapidly become systemic, but there seems no a priori reason why haematopoietic cells should behave any differently from other somatic cells in this respect. The absence of dominantly inherited forms may indicate that this kind of mechanism is unlikely for both leukaemias and lymphomas. Increased probability of initiation There is little evidence that any inherited cancer prone condition depends upon an unusual interaction between a carcinogenic agent and the DNA of the cell. Variation depends rather upon the way in which the carcinogen is handled prior to interaction with the DNA and upon the way in which induced DNA damage is handled. Both are clearly under genetic control. Many potentially carcinogenic chemicals require metabolic activation for the carcinogenic properties to be realized. There are many examples of genetic control of the activation process, e.g. the inducibility of enzymes controlling the metabolism of polycyclic hydrocarbon carcinogens^. Until recently there had been little evidence of leukaemia inducation in man by chemical carcinogens. However, convincing reports of acute leukaemia following long-term cytotoxic therapy^ now make it particularly important to elucidate the mechanisms by which drugs induce leukaemias in a proportion of patients. Similarly, there is a clear association between the degree of skin pigmentation and the induction of all types of skin cancer. Therefore the effect of UV irradiation is modified before it reaches the target cell by a genetically controlled characteristic. Once again, however, there is no evidence for a role for UV in leukaemogenesis but the principle is still an important one. In some inherited human cancer prone diseases, an unusual susceptibility to an environmental agent is thought to be due to events occurring after the primary interactions between the agent and the cellular DNA. In particular, defects in repair of DNA lesions have been implicated. In xeroderma pigmentosum, for example, defects of DNA repair, increased mutagenesis and carcinogens following exposure to UV light are clearly associated^ In other diseases, where defects of DNA repair have been suggested as explanations of increased susceptibility to leukaemia or lymphoma, the association is not clear cut. The complexities are best studied by considering one specific example - ataxia telangiectasia (see below). Susceptibility to progression Once again there is compelling circumstantial evidence that the progression of a focus of neoplastic cells towards malignancy will be influenced by factors under genetic control, for example, hormone balance, immune response and so on. There are, however, remarkably few well documented cases. For example, there is good evidence that patients with inherited immunodeficiency syndromes have an unusual tendency to develop leukaemias and lymphomas.