Receptor tyrosine kinase AXL is induced by chemotherapy drugs and overexpression of AXL confers drug resistance in acute myeloid leukemia
Journal
Cancer letters
Journal Volume
268
Journal Issue
2
Pages
314-324
Date Issued
2008
Author(s)
Abstract
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. ? 2008 Elsevier Ireland Ltd. All rights reserved.
SDGs
Other Subjects
antineoplastic agent; cisplatin; doxorubicin; etoposide; growth arrest specific protein 6; mitogen activated protein kinase 1; mitogen activated protein kinase 3; protein bcl 2; protein tyrosine kinase; receptor tyrosine kinase axl; transcription factor Twist; acute granulocytic leukemia; article; cancer resistance; cell strain U937; controlled study; drug sensitivity; enzyme activation; human; human cell; priority journal; promoter region; protein expression; protein methylation; protein phosphorylation; upregulation; Antineoplastic Agents; Base Sequence; Drug Resistance, Neoplasm; Humans; Intercellular Signaling Peptides and Proteins; Leukemia, Myeloid, Acute; Molecular Sequence Data; Oncogene Proteins; Promoter Regions (Genetics); Receptor Protein-Tyrosine Kinases; Signal Transduction; U937 Cells
Type
journal article