Sai Shuji, Nakagawa Yuichi, Sakaguchi Kimiyoshi, Okada Shuichi, Takahashi Hiroyoshi, Hongo Teruaki, Seckl Jonathan R, Chapman Karen E, Ohzeki Takehiko
Department of Pediatrics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
Leuk Res. 2009 Dec;33(12):1696-8. doi: 10.1016/j.leukres.2009.04.016. Epub 2009 May 14.
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.
糖皮质激素疗法是儿童急性淋巴细胞白血病（ALL）至关重要的一线治疗方法。然而，糖皮质激素抵抗是一个治疗难题，其分子机制尚不清楚。11β-羟基类固醇脱氢酶-1（11β-HSD1）在糖皮质激素靶组织中表达，在该组织中它可将惰性的11-酮糖皮质激素再生为活性糖皮质激素，从而放大细胞内糖皮质激素水平。在此，我们展示了11β-HSD1在ALL患者（n = 14）白血病细胞中的表达情况。在糖皮质激素敏感和耐药的ALL细胞之间，糖皮质激素对11β-HSD1的调节存在差异。地塞米松可增加糖皮质激素敏感ALL细胞中11β-HSD1的mRNA水平，但在耐药组中则降低其水平。我们的数据表明，11β-HSD1的差异诱导作用与白血病中糖皮质激素敏感性有关。
