Dysfunctional glucocorticoid receptors in acute leukemia.

The obligatory role of specific cytoplasmic receptors as mediators of steroid hormone action is well established. In lymphoid cell culture Systems the development or glucocorticoid resistance is almost always due to a mutation to a receptor negative state [I]. Therefore, if the assumption is that glucocorticoid-induced remission in leukemia is by a direct effect on leukemic blast cells, one would predict that the presence of absence of blast cell glucocorticoid receptors would be a major determinant or clinical steroid sensitivity. However, receptor quantization has not correlated with steroid responsiveness [2-51, and in particular, high receptor numbers are not uniformly associated with responsive disease [6] . We have speculated that this lack of concordance between receptor Status and clinical outcome may be due to the presence of glucocorticoid binding macromolecules which are physiologically nonfunctional in those leukemias which are glucocorticoid resistant. To test this hypothesis, we have studied certain biochemical and biophysical characteristics of glucocorticoid binders in normal and leukemia cells, to determine if such dysfunctional binding macromolecules exist, and to establish their relationship to therapeutic outcome. B. Materials and Methods