The purpose of these studies is to apply our current knowledge regarding glucocorticoid receptors and mechanism of action in lymphoid cells towards understanding the therapeutic actions of glucocorticoids in the treatment of lymphocytic and myelocytic leukemias. In particular, we are interested in elucidating the differences between glucocorticoid-sensitive and resistant leukemias. To this end, we will test lymphocytes from leukemic patients for: (a) the presence of cytoplasmic and nuclear glucocorticoid receptors; (b) the ability of the cytoplasmic hormone-receptor complexes to undergo cytoplasmic-nuclear translocation; (c) sensitivity to glucocorticoids with respect to several metabolic parameters including inhibition of protein synthesis, nucleic acid synthesis and glucose metabolism; (d) sensitivity to glucocorticoids with respect to survival. The results of these tests will be correlated, where possible, with the clinical course of treatment, and will also serve as points of departure for deeper studies with selected cell populations on nuclear acceptor sites, nuclear and plasma membrane structure and cell surface antigens. In parallel work we will study normal human, mouse, and rat lymphocytes with respect to some of the same glucocorticoid-related properties. These cells, furthermore, as well as macrophages, will be used to investigate glucocorticoid effects on calcium uptake, on induction of viruses and expression of cell surface antigens. Significant results from these latter studies will be applied to the work with leukemic cells, and vice versa.
NIH ExPorter
NIH ExPorter