BCRP gene expression is associated with a poor response to remission induction therapy in childhood acute myeloid leukemia
BCRP gene expression is associated with a poor response to remission induction therapy in childhood acute myeloid leukemia
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DOI：
10.1038/sj.leu.2402541
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发表时间：
2002-08-01
期刊：
影响因子：
11.4
通讯作者：
Sauerbrey, A
中科院分区：
文献类型：
--
作者：
Steinbach, D;Sell, W;Sauerbrey, A
乳腺癌耐药蛋白（BCRP），也称为米托蒽醌耐药蛋白（MRX）或胎盘ABC蛋白（ABC-P），是ABC转运蛋白ABCG亚家族的第二个成员（基因符号ABCG 2）。BCRP在药物敏感细胞中的转染和增强表达赋予对米托蒽醌、阿霉素、柔红霉素和拓扑替康的抗性。本研究采用TaqMan实时荧光定量PCR技术检测了59例初治AML患儿BCRP基因的表达。9例患者也在复发中进行了分析。在第一阶段化疗后未达到缓解的患者（n = 24）中，BCRP基因表达的中位数是在该阶段达到缓解的患者（n = 21; P = 0.012）的10倍以上。首次复发时BCRP基因表达高于诊断时（P = 0.038）。虽然高水平的BCRP基因表达在预后良好的AML亚型中更常见，但我们发现在两个风险组（高风险和低风险）中，表达高水平BCRP的患者预后较差（P = 0.023）。我们的研究结果强烈提示BCRP基因的表达降低了AML对化疗的反应，并且BCRP表达在复发时更高。
Breast cancer resistance protein (BCRP), also known as mitoxantrone resistance protein (MRX) or placenta ABC protein (ABC-P), is the second member of the ABCG subfamily of ABC transport proteins (gene symbol ABCG2). Transfection and enforced expression of BCRP in drug-sensitive cells confers resistance to mitoxantrone, doxorubicin, daunorubicin and topotecan. In this study the expression of BCRP gene was measured using TaqMan real-time PCR in 59 children with newly diagnosed AML. Nine patients were also analyzed in relapse. The median of BCRP gene expression was more than 10 times higher in patients who did not achieve remission after the first phase of chemotherapy (n = 24) as compared to patients who did achieve remission at this stage (n = 21; P = 0.012). In first relapse the expression of the BCRP gene was higher than at diagnosis (P = 0.038). Although high levels of BCRP gene expression were more frequent in subtypes of AML with a favorable prognosis, we found that within both risk groups (high and low risk), patients who expressed high levels of BCRP had a worse prognosis (P = 0.023). Our results strongly suggest that the expression of the BCRP gene reduces the response to chemotherapy in AML and that BCRP expression is higher at the time of relapse.