Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells
Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells
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DOI：
10.1038/ng1151
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发表时间：
2003-05-01
期刊：
影响因子：
30.8
通讯作者：
Evans, WE
中科院分区：
文献类型：
--
作者：
Cheok, MH;Yang, WL;Evans, WE
为了阐明细胞对癌症治疗的反应的基因组学，我们分析了在单独或联合给予甲氨蝶呤和巯基嘌呤的体内治疗前后急性淋巴细胞白血病细胞中超过9，600个人类基因的表达。基于基因表达的变化，我们确定了124个基因，准确区分四种治疗。鉴别基因包括那些参与细胞凋亡、错配修复、细胞周期控制和应激反应的基因。当这些药物作为单一药物给予时，只有14%的基因发生了变化，当它们一起给予时也发生了变化。这些数据表明，不同分子亚型的淋巴样白血病细胞对相同治疗有共同的基因组应答途径，基因表达的变化具有治疗特异性，基因表达可以说明细胞对药物组合与单一药物的应答差异。
To elucidate the genomics of cellular responses to cancer treatment, we analyzed the expression of over 9,600 human genes in acute lymphoblastic leukemia cells before and after in vivo treatment with methotrexate and mercaptopurine given alone or in combination. Based on changes in gene expression, we identified 124 genes that accurately discriminated among the four treatments. Discriminating genes included those involved in apoptosis, mismatch repair, cell cycle control and stress response. Only 14% of genes that changed when these medications were given as single agents also changed when they were given together. These data indicate that lymphoid leukemia cells of different molecular subtypes share common pathways of genomic response to the same treatment, that changes in gene expression are treatment-specific and that gene expression can illuminate differences in cellular response to drug combinations versus single agents.