Glucocorticoid receptors and effects in human lymphoid and leukemic cells

Abstract

A variety of human leukopathic diseases including human acute lymphoblastic leukemia are responsive to glucocorticoids in a varying proportion of cases. We identified specific glucocorticoid receptors in human acute lymphoblastic leukemia cells. Their presence or absence was well correlated with both in vivo and in vitro responsiveness of these target cells to glucocorticoids. These data suggest that knowledge of glucocorticoid receptor status in human acute lymphoblastic leukemia may aid in selecting patients for therapy. Furthermore, these receptors exhibit significant quantitative differences in various subtypes of human leukemia, with null-cell lymphoblastic leukemia having approximately three times the mean number of receptors per cell as T-cell leukemias. These differences in receptor levels are associated with major differences in complete remission duration independent of other prognosticators of response such as patient age, white count, and cell surface markers. Specific receptors for glucocorticoids can also be identified in normal human peripheral blood monocyte fractions including unpurified peripheral blood lymphocytes, T, and non-T subcomponents of circulating lymphocytes and circulating monocytes. By criteria of quantity, of binding affinity, and specificity, these receptors appear to be similar to other classical glucocorticoid receptors. Receptors in human peripheral blood lymphocytes may be induced threefold on a per cell basis by treatment with the mitogen phytohemagglutinin. This is associated with a marked increase in glucocorticoid responsiveness.