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

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

doi:10.1016/j.leukres.2009.04.016

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

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

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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. 11beta-Hydroxysteroid dehydrogenase-1 (11beta-HSD1) is expressed in glucocorticoid target tissue, where it regenerates active glucocorticoids from inert 11keto-glucocorticoids, amplifying intracellular glucocorticoid levels. Here, we show 11beta-HSD1 expression in leukemic cells from ALL patients (n=14). 11beta-HSD1 was differentially regulated by glucocorticoids between glucocorticoid-sensitive and -resistant ALL cells. Dexamethasone increased 11beta-HSD1 mRNA levels in glucocorticoid-sensitive ALL cells, but decreased levels in the resistant group. Our data suggest that differential induction of 11beta-HSD1 contributes to the glucocorticoid sensitivity in leukemia.

Original language	English
Pages (from-to)	1696-8
Number of pages	3
Journal	Leukemia Research
Volume	33
Issue number	12
DOIs	https://doi.org/10.1016/j.leukres.2009.04.016
Publication status	Published - 2009

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10.1016/j.leukres.2009.04.016

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title = "Differential regulation of 11beta-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. 11beta-Hydroxysteroid dehydrogenase-1 (11beta-HSD1) is expressed in glucocorticoid target tissue, where it regenerates active glucocorticoids from inert 11keto-glucocorticoids, amplifying intracellular glucocorticoid levels. Here, we show 11beta-HSD1 expression in leukemic cells from ALL patients (n=14). 11beta-HSD1 was differentially regulated by glucocorticoids between glucocorticoid-sensitive and -resistant ALL cells. Dexamethasone increased 11beta-HSD1 mRNA levels in glucocorticoid-sensitive ALL cells, but decreased levels in the resistant group. Our data suggest that differential induction of 11beta-HSD1 contributes to the glucocorticoid sensitivity in leukemia.",

author = "Shuji Sai and Yuichi Nakagawa and Kimiyoshi Sakaguchi and Shuichi Okada and Hiroyoshi Takahashi and Teruaki Hongo and Seckl, {Jonathan R} and Chapman, {Karen E} and Takehiko Ohzeki",

year = "2009",

doi = "10.1016/j.leukres.2009.04.016",

language = "English",

volume = "33",

pages = "1696--8",

journal = "Leukemia Research",

publisher = "Elsevier",

number = "12",

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TY - JOUR

T1 - Differential regulation of 11beta-hydroxysteroid dehydrogenase-1 by dexamethasone in glucocorticoid-sensitive and -resistant childhood lymphoblastic leukemia

AU - Sai, Shuji

AU - Nakagawa, Yuichi

AU - Sakaguchi, Kimiyoshi

AU - Okada, Shuichi

AU - Takahashi, Hiroyoshi

AU - Hongo, Teruaki

AU - Seckl, Jonathan R

AU - Chapman, Karen E

AU - Ohzeki, Takehiko

PY - 2009

Y1 - 2009

N2 - 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. 11beta-Hydroxysteroid dehydrogenase-1 (11beta-HSD1) is expressed in glucocorticoid target tissue, where it regenerates active glucocorticoids from inert 11keto-glucocorticoids, amplifying intracellular glucocorticoid levels. Here, we show 11beta-HSD1 expression in leukemic cells from ALL patients (n=14). 11beta-HSD1 was differentially regulated by glucocorticoids between glucocorticoid-sensitive and -resistant ALL cells. Dexamethasone increased 11beta-HSD1 mRNA levels in glucocorticoid-sensitive ALL cells, but decreased levels in the resistant group. Our data suggest that differential induction of 11beta-HSD1 contributes to the glucocorticoid sensitivity in leukemia.

AB - 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. 11beta-Hydroxysteroid dehydrogenase-1 (11beta-HSD1) is expressed in glucocorticoid target tissue, where it regenerates active glucocorticoids from inert 11keto-glucocorticoids, amplifying intracellular glucocorticoid levels. Here, we show 11beta-HSD1 expression in leukemic cells from ALL patients (n=14). 11beta-HSD1 was differentially regulated by glucocorticoids between glucocorticoid-sensitive and -resistant ALL cells. Dexamethasone increased 11beta-HSD1 mRNA levels in glucocorticoid-sensitive ALL cells, but decreased levels in the resistant group. Our data suggest that differential induction of 11beta-HSD1 contributes to the glucocorticoid sensitivity in leukemia.

U2 - 10.1016/j.leukres.2009.04.016

DO - 10.1016/j.leukres.2009.04.016

M3 - Article

C2 - 19446331

VL - 33

SP - 1696

EP - 1698

JO - Leukemia Research

JF - Leukemia Research

IS - 12

ER -

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

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