Differential regulation of 11β-hydroxysteroid dehydrogenase-1 by dexamethasone in glucocorticoid-sensitive and -resistant childhood lymphoblastic leukemia☆
Received 16 February 2009; received in revised form 16 February 2009; accepted 14 April 2009.
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.
aDepartment of Pediatrics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan
bDepartment of Pediatrics, Iwata City Hospital, Iwata 438-8550, Japan
cEndocrinology Unit, Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom
ABSTRACT