Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia
Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia
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DOI：
10.1182/blood-2011-04-351239
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发表时间：
2011-08-25
期刊：
影响因子：
20.3
通讯作者：
Kim, Yong-Mi
中科院分区：
文献类型：
--
作者：
Park, Eugene;Gang, Eun Ji;Kim, Yong-Mi
耐药急性淋巴细胞白血病（ALL）的复发与凋亡蛋白抑制剂生存素/BIRC 5的表达增加有关，这表明ALL细胞具有生存优势。在本研究中，我们报告说，抑制生存素在患者源性ALL可以根除白血病。在原发性ALL的异种移植模型中，靶向survivin的shRNA联合化疗导致未检测到微小残留疾病。类似地，使用EZN-3042（一种新的锁核酸反义寡核苷酸）的存活素的药理学敲低与化疗组合消除了耐药ALL细胞。这些发现显示了生存素表达在耐药性中的重要性，并表明生存素抑制可能是克服ALL患者耐药性和预防复发的有力方法。（血。2011;118（8）：2191-2199）
Relapse of drug-resistant acute lymphoblastic leukemia (ALL) has been associated with increased expression of survivin/BIRC5, an inhibitor of apoptosis protein, suggesting a survival advantage for ALL cells. In the present study, we report that inhibition of survivin in patient-derived ALL can eradicate leukemia. Targeting survivin with shRNA in combination with chemotherapy resulted in no detectable minimal residual disease in a xenograft model of primary ALL. Similarly, pharmacologic knock-down of survivin using EZN-3042, a novel locked nucleic acid antisense oligonucleotide, in combination with chemotherapy eliminated drug-resistant ALL cells. These findings show the importance of survivin expression in drug resistance and demonstrate that survivin inhibition may represent a powerful approach to overcoming drug resistance and preventing relapse in patients with ALL. (Blood. 2011;118(8):2191-2199)