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

Sai, Shuji; Nakagawa, Yuichi; Sakaguchi, Kimiyoshi; Okada, Shuichi; Takahashi, Hiroyoshi; Hongo, Teruaki; Seckl, Jonathan R.; Chapman, Karen E.; Ohzeki, Takehiko

doi:10.1016/j.leukres.2009.04.016

« Previous Next »Leukemia Research
Volume 33, Issue 12 , Pages 1696-1698, December 2009

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

Shuji Sai
- Department of Pediatrics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan
- Corresponding author. Tel.: +81 53 435 2312; fax: +81 53 435 2311.
Yuichi Nakagawa
- Department of Pediatrics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan
Kimiyoshi Sakaguchi
- Department of Pediatrics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan
Shuichi Okada
- Department of Pediatrics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan
Hiroyoshi Takahashi
- Department of Pediatrics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan
Teruaki Hongo
- Department of Pediatrics, Iwata City Hospital, Iwata 438-8550, Japan
Jonathan R. Seckl
- Endocrinology Unit, Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom
Karen E. Chapman
- Endocrinology Unit, Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom
Takehiko Ohzeki
- Department of Pediatrics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan

Received 16 February 2009; received in revised form 16 February 2009; accepted 14 April 2009. published online 07 March 2011.

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.