Therapeutic and prognostic implications of glucocorticoid receptors and terminal deoxynucleotidyl transferase in acute leukemia

Abstract

Glucocorticoid receptors (GR) have been reported to predict clinical responsiveness to glucocorticoid therapy and to possess prognostic significance in leukemia. A raised level in terminal deoxynucleotidyl transferase (TdT) also seems to suggest clinical responsiveness to prednisone and vincristine therapy. We have investigated these two biochemical markers in the leukemic blasts in 23 patients with acute myeloid leukemia (AML) and in 19 patients with acute lymphoblastic leukemia (ALL) and have compared the binding data with clinical glucocorticoid sensitivity. with response to chemotherapy, with survival and with TdT. In 25 of these patients we have also investigated the in vitro glucocorticoid sensitivity by measuring dexamethasone inhibition of radiolabelled uridine and thymidine incorporation into the leukemic blasts. In patients with AML. GR levels were mostly high but did not correlate with the in vitro sensitivity. response to chemotherapy or survival. On the other hand, in the 19 patients with ALL there seemed to be a correlation between GR and in vitro sensitivity and between GR and clinical responsiveness to glucocorticoid therapy. Furthermore, patients with low levels of either TdT or GR seemed to be associated with poor prognosis. TdT activity and GR, however, did not associate with one another. TdT is a useful marker for the identification of lymphoblasts but, by itself, is not connected with glucocorticoid sensitivity. GR, when applied to ALL. could supplement TdT determination by predicting response to therapy.