Glucocorticoid receptor and in vitro sensitivity to steroid hormones in human lymphoproliferative diseases and myeloid leukemia.
The glucocorticoid receptor (GR) quantitation by a whole-cell assay and/or cytosol technique and the in vitro sensitivity to steroids have been assessed in peripheral blood cells from normal donors and patients with chronic lymphatic leukemia (CLL), acute lymphoblastic leukemia (ALL), lymphosarcoma cell leukemia (LSCL), acute nonlymphatic leukemia (ANLL), and chronic myeloid leukemia (CML). Within the lymphoproliferative diseases, ALL cells exhibited the highest GR concentration (regardless of the method used) and the highest in vitro inhibition of spontaneous [3H]thymidine ([3H]TdR) uptake by glucocorticoids. A significant relationship between GR concentration (whole-cell assay) and in vitro sensitivity to dexamethasone was also found. On the contrary, CLL cells presented the highest sensitivity to glucocorticoids in PHA-stimulated cell cultures. Cells from the only two ALL patients who did not undergo a remission after glucocorticoid-inclusive chemotherapy had both the lowest in vitro sensitivity to dexamethasone and the lowest GR concentration with whole-cell assay. Concerning myeloid leukemia, ANLL patients had GR concentrations slightly higher than those found in the ALL group but exhibited the lowest degree of inhibition of spontaneous [3H]TdR uptake by dexamethasone (stimulatory effects occurred in some cases). CML cells exhibited an inhibition degree by in vitro glucocorticoids significantly higher than that of ANLL cells but not different from that of lymphoproliferative diseases. No clear relationship among GR pattern, in vitro cell sensitivity to glucocorticoids, and clinicohematologic parameters was observed in myeloid leukemia-bearing patients.
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D006889:Hydroxycorticosteroids / Q000494:pharmacology*; D007945:Leukemia, Lymphoid / Q000097:blood*; D007951:Leukemia, Myeloid / Q000097:blood*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D011239:Prednisolone / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000032:analysis / Q000187:drug effects*; D011987:Receptors, Steroid / Q000187:drug effects*; D013760:Tetrahydrocortisol / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D006889:Hydroxycorticosteroids; D008934:Mitogens; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D013760:Tetrahydrocortisol; D003907:Dexamethasone; D011239:Prednisolone; D013936:Thymidine; D006854:Hydrocortisone