Differential regulation of 11β-hydroxysteroid dehydrogenase-1 by dexamethasone in glucocorticoid-sensitive and -resistant childhood lymphoblastic leukemia

Abstract Glucocorticoid therapy forms a crucial first-line treatment for childhood acute lymphoblastic leukemia (ALL). However, glucocorticoid resistance is a therapeutic problem with an unclear molecular mechanism. 11β-Hydroxysteroid dehydrogenase-1 (11β-HSD1) is expressed in glucocorticoid target tissue, where it regenerates active glucocorticoids from inert 11keto-glucocorticoids, amplifying intracellular glucocorticoid levels. Here, we show 11β-HSD1 expression in leukemic cells from ALL patients ( n = 14). 11β-HSD1 was differentially regulated by glucocorticoids between glucocorticoid-sensitive and -resistant ALL cells. Dexamethasone increased 11β-HSD1 mRNA levels in glucocorticoid-sensitive ALL cells, but decreased levels in the resistant group. Our data suggest that differential induction of 11β-HSD1 contributes to the glucocorticoid sensitivity in leukemia.