Glucocorticoid receptors and sensitivity of isolated human leukemia and lymphoma cells.

In an attempt to lay a sound foundation for understand ing the therapeutic effectiveness of glucocorticoids in the treatment of hematological cancers, we have studied glucocorticoid receptors and sensitivity to glucocorticoids in vitro in the malignant cells from 56 patients with leuke mia and lymphoma and in peripheral lymphocytes from normal donors. In contrast to several previous studies in which myeloblasts and lymphocytes from patients with chronic lymphocytic leukemia were reported to lack glu cocorticoid receptors, we have found that with a wholecell assay there is saturable binding of dexamethasone in all cases, with 400 to 13,230 nuclear binding sites/cell. These binding sites were similar in all respects studied to those of glucocorticoid receptors in the normal lympho cytes and other cell types. Supporting a physiological role for these receptors, normal lymphocytes and cells of 42 of 43 patients tested (including 5 of 5 with acute lymphocytic leukemia, 10 of 10 with chronic lymphocytic leukemia, and 17 of 18 with acute nonlymphocytic leukemia or chronic myelocytic leukemia in blast crisis) showed dose-depend ent effects of glucocorticoids in vitro of glucose transport and L-leucine, uridine, or thymidine incorporation. In 38 of 44 cases and in the normal lymphocytes, cell death or impairment of proliferation was noted. Greatest sensitivity was exhibited by cells from patients with acute and chronic lymphocytic leukemia and lymphoma. These results indicate that cells of all hematological cancers have receptors for glucocorticoids and that vari ations in clinical sensitivity to glucocorticoid therapy are not related to the presence or absence of the receptor as has been proposed previously.