Receptor tyrosine kinase AXL is induced by chemotherapy drugs and overexpression of AXL confers drug resistance in acute myeloid leukemia
Receptor tyrosine kinase AXL is induced by chemotherapy drugs and overexpression of AXL confers drug resistance in acute myeloid leukemia
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DOI：
10.1016/j.canlet.2008.04.017
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发表时间：
2008-09-18
期刊：
影响因子：
9.7
通讯作者：
Chuang, Shuang-En
中科院分区：
文献类型：
--
作者：
Hong, Chih-Chen;Lay, Jong-Ding;Chuang, Shuang-En
通过对同一患者的敏感性和难治性白血病中差异表达的蛋白酪氨酸激酶进行新的谱分析，我们发现耐药白血病中AXL上调。此外，化疗药物可诱导急性髓系白血病U937细胞中的AXL，并且这种诱导依赖于AXL启动子的CCWGG甲基化状态。在异位过表达AXL的U937细胞中，加入外源性Gas 6诱导AXL磷酸化和Akt和ERK 1/2存活通路的激活。耐药的Gas 6-AXL活化途径与Bcl-2和Twist表达增加有关。这些结果表明，在Gas 6刺激存在下，化疗对AXL的上调可能诱导急性髓性白血病的耐药性。(c)2008爱思唯尔爱尔兰有限公司保留所有权利。
By using a novel profiling analysis of protein tyrosine kinases differentially expressed in the sensitive and refractory leukemia from the same patients we found that AXL was upregulated in drug-resistant leukemia. Furthermore, AXL could be induced by chemotherapy drugs in the acute myeloid leukemia U937 cells and this induction,vas dependent on the CCWGG methylation status of the AXL promoter. In U937 cells ectopically overexpressing AXL, addition of exogenous Gas6 induced AXL phosphorylation and activation of the Akt and ERK1/2 survival pathways. The Gas6-AXL activation pathway of drug resistance was associated with increased expression of Bcl-2 and Twist. These results show that upregulation of AXL by chemotherapy might induce drug, resistance in acute myeloid leukemia in the presence of Gas6 stimulation. (c) 2008 Elsevier Ireland Ltd. All rights reserved.