Glucocorticoid receptors in lymphoid tumors.

There is a range of levels of glucocorticoid receptor numbers seen in the various subclasses of acute lymphatic leukemia (ALL). This variability cannot be explained by the known correlation between active cell proliferation and an increase in the number of receptors, since the tumors with the highest growth fraction (i.e., Burkitt's lymphoma and T-cell leukemia) tend to have lower average receptor numbers than do tumors with lower growth fractions such as common ALL. All clinical specimens from patients with lymphatic leukemia have some measurable level of glucocorticoid receptors; therefore, the resistance seen in vivo cannot be explained by the lack of receptors. However, there has been a positive correlation, in our hands, with receptor level and prognosis. On the basis of in vitro models, it is proposed that perhaps the high receptor cell lines (i.e., common ALL of childhood) have relative stability of their genetic material making glucocorticoid-resistant mutations less likely to occur in patients with these cells than in low-receptor cell lines (i.e., T-cell leukemia). This greater genetic variability in the low-receptor lines could account for the earlier emergence of clinical glucocorticoid resistance in these patients.