Glucocorticoid-induced granzyme A expression can be used as a marker of glucocorticoid sensitivity for acute lymphoblastic leukemia therapy
Glucocorticoid-induced granzyme A expression can be used as a marker of glucocorticoid sensitivity for acute lymphoblastic leukemia therapy
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DOI：
10.1007/s10038-007-0119-4
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发表时间：
2007-04-01
影响因子：
3.5
通讯作者：
Tsujimoto, Gozoh
中科院分区：
文献类型：
--
作者：
Myoumoto, Akira;Nakatani, Kaoru;Tsujimoto, Gozoh
糖皮质激素（GC）有效杀死淋巴细胞的能力已经导致它们被包括在基本上所有用于治疗急性淋巴细胞白血病（all）的化疗程序中。GC敏感性是ALL治疗中重要的预后因素，并用于将患者划分为危险组。然而，临床评估气相色谱敏感性是非常耗时的。我们最近发现颗粒酶A （GZMA）介导gc诱导的all来源细胞系697细胞凋亡。在这项研究中，我们使用来自ALL患者的7个已建立的细胞系检测了GC敏感性与GC诱导的GZMA表达之间的相关性。凋亡试验显示4株细胞株气相色谱敏感，3株气相色谱耐药。GC处理仅在GC敏感细胞株中显著提高GZMA的表达，而在GC耐药细胞株中无显著提高。gc诱导的GZMA表达也与gc诱导的细胞凋亡数量密切相关。因此，gc诱导的GZMA表达可能是一种有用的“个性化”ALL治疗的早期生物标志物。
The ability of glucocorticoids (GC) to efficiently kill lymphoid cells has led to their inclusion in essentially all chemotherapy procedures used to treat acute lymphoblastic leukemia (ALL). GC sensitivity is an important prognostic factor in ALL treatment, and it is used to classify patients into risk groups. Clinical assessment for GC sensitivity is very time-consuming, however. We have recently found that granzyme A (GZMA) mediates GC-induced apoptosis in ALL-derived cell line 697. In this study we examined the correlation between GC sensitivity and GC-induced GZMA expression by using seven established cell lines derived from ALL patients. The apoptosis assay showed four cell lines were GC-sensitive and three were GC-resistant. GC treatment markedly enhanced GZMA expression in GC-sensitive cell lines only, and not in GC-resistant cell lines. GC-induced GZMA expression also correlated well with the amount of GC-induced apoptosis. GC-induced GZMA expression could thus be a useful early biomarker for "personalized" ALL therapy.