Glucocorticoid resistance in childhood leukemia

Glucocorticoid resistance is frequently encountered in childhood leukemia, especially in relapsed acute lymphoblastic leukemia and acute-non-lymphoblastic leukemia but also in newly diagnosed acute lymphoblastic leukemia. Glucocorticoid resistance is associated with a relatively poor prognosis. Therefore, studies on mechanisms of glucocorticoid resistance and modulation or circumvention of such resistance are of major clinical importance. Such studies on clinical specimens so far have focused on glucocorticoid receptors, showing that a low receptor number is associated with a less favorable response to glucocorticoid treatment and a relatively poor prognosis after combination chemotherapy. However, a high receptor number does not warrant responsiveness to glucocorticoids. This review summarizes our current knowledge of mechanisms of glucocorticoid resistance and possibilities to modulate or circumvent that resistance. This knowledge is mainly based on cell line studies, but these have yielded most interesting results. Therefore, clinical studies and laboratory studies using clinical leukemia specimens should be intensified.