Glucocorticoid receptors and hormonal responsiveness of human blood and bone-marrow cells in non-lymphocytic leukemia

Abstract

In man, acute non lymphoid leukemia (ANLL) bas been shown to respond in an extremely variable manner to glucocorticoid therapy. In addition to glucocorticoids. other agents such as β-adrenergic agents and prostaglandins are known to modulate the proliferation and differentiation of granulocyte monocyte colonies (CFU-C). We have measured in vitro on the blood and bone-marrow cells from three patients with ANLL several parameters including glucocorticoid receptors, the percentage of cells in the S phase of the cell cycle (using pulse cytophotometry) and the effect of drugs on nucleoside incorporation, cell number and viability. Our results led to the following conclusions: (i) The examination of blood and bone-marrow samples of a given patient does not necessarily give similar results in terms of response to drugs and the level of glucocorticoid receptors, (ii) in the same patient, the effect of any agent varies greatly throughout the incubation period and is also variable from one subpopulation to another, (iii) Prostaglandin E 2 markedly enhanced the level of [ 3H]-thymidine incorporation in the patients tested. As steroid-induced prostaglandin production has been recently implicated in the differentiation of myeloid cells, this may explain the stimulatory action of glucocorticoids which has been observed both in vivo and in vitro in ANLL patients.