Search

In this paper we have briefly reviewed the nature of leukemias and lymphomas in the old and the young. We surveyed in general the ways in which lymphoid cells and other hematologic elements respond to glucocorticoids, mentioning that there may be direct or indirect effects on their growth by these ligands. We have reviewed the current general model for the action of glucocorticoids in all cells, namely the fact that the actions of these steroids are mediated to a large extent through binding with ligand-activated transcription factors, their receptors. The growing wealth of detail about the nature of the interaction of these receptors with regulatory sites in the genome is discussed. Finally, we have described our results with lines of tissue culture cells representing clones from a typical leukemia of the young, and of myeloma, a typical hematologic malignancy of the elderly. Several features of the effects of glucocorticoids on these cells point up areas that would be pertinent to explore in aging and in the relationship of hematologic diseases to survival and response to therapy in the older versus the younger patient.

Clinical measurements quantitating glucocorticoid receptor sites in leukemic blasts may give useful prognostic information. In childhood ALL, where the most data is available, "high" receptor content in peripheral or marrow blasts correlated with likelihood of remission on therapy, longer durations of remission and better prognosis generally. In lymphomas and CLL as well, high receptor content correlated with likelihood of response to steroid therapy, though the number of studies is less. In AML the correlation with receptor site content is moot, and in other leukemias the reports are less complete. A model system for childhood ALL is provided by CEM cells, a glucocorticoid sensitive human cell line from a patient with the disease. These cells have glucocorticoid receptors which must be filled by hormone for greater than 24 hr for cell lysis to begin. Four types of glucocorticoid resistance have been identified thus far in clones of these cells. Their distinctive properties are described and their relevance to clinical situations briefly discussed.