Glucocorticoid Receptors and Resistance to Glucocorticoids in Hematologic Malignancies

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Abstract
Glucocorticoids are highly effective in inducing the cytolysis of cells of lymphocytic origin. This property has resulted in their incorporation into chemotherapy regimens used in the treatment of hematologic malignancies. Studies at the molecular and cellular levels have demonstrated that the hormone-induced cytolytic response is mediated through a highly specific cytoplasmic glucocorticoid receptor (GR). The GR has been cloned and sequenced and found to be organized into a discrete series of domains which mediate the receptor functions of hormone binding, nuclear translocation, DNA binding and transcriptional modulation. Thus, the binding of glucocorticoids by the GR induces a series of cellular events which result in the activation or repression of a network of glucocorticoid responsive genes and produces a specific cellular response.