Receptor tyrosine kinase AXL is induced by chemotherapy drugs and overexpression of AXL confers drug resistance in acute myeloid leukemia

Chih Chen Hong, Jong Ding Lay, Jhy Shrian Huang, Ann Lii Cheng, Jih Luh Tang, Ming Tseh Lin, Gi Ming Lai, Shuang En Chuang

研究成果: 雜誌貢獻文章

121 引文 (Scopus)

摘要

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 was 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.

原文英語
頁(從 - 到)314-324
頁數11
期刊Cancer Letters
268
發行號2
DOIs
出版狀態已發佈 - 九月 18 2008
對外發佈Yes

指紋

U937 Cells
Receptor Protein-Tyrosine Kinases
Drug Resistance
Acute Myeloid Leukemia
Leukemia
Drug Therapy
MAP Kinase Signaling System
Pharmaceutical Preparations
Protein-Tyrosine Kinases
Methylation
Up-Regulation
Phosphorylation
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

引用此文

Receptor tyrosine kinase AXL is induced by chemotherapy drugs and overexpression of AXL confers drug resistance in acute myeloid leukemia. / Hong, Chih Chen; Lay, Jong Ding; Huang, Jhy Shrian; Cheng, Ann Lii; Tang, Jih Luh; Lin, Ming Tseh; Lai, Gi Ming; Chuang, Shuang En.

於: Cancer Letters, 卷 268, 編號 2, 18.09.2008, p. 314-324.

研究成果: 雜誌貢獻文章

Hong, Chih Chen ; Lay, Jong Ding ; Huang, Jhy Shrian ; Cheng, Ann Lii ; Tang, Jih Luh ; Lin, Ming Tseh ; Lai, Gi Ming ; Chuang, Shuang En. / Receptor tyrosine kinase AXL is induced by chemotherapy drugs and overexpression of AXL confers drug resistance in acute myeloid leukemia. 於: Cancer Letters. 2008 ; 卷 268, 編號 2. 頁 314-324.
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AU - Hong, Chih Chen

AU - Lay, Jong Ding

AU - Huang, Jhy Shrian

AU - Cheng, Ann Lii

AU - Tang, Jih Luh

AU - Lin, Ming Tseh

AU - Lai, Gi Ming

AU - Chuang, Shuang En

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AB - 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 was 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.

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KW - Gas6

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