2017 Fiscal Year Final Research Report
The elucidation of the mechanism of imatinib-resistance in CML stem cells using disease specific iPSCs
| Project/Area Number |
16K19568
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | 疾患由来iPS細胞 / 慢性骨髄性白血病 / がん幹細胞 |
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| Outline of Final Research Achievements |
Properties of cancer stem cells (CSC) involved in drug-resistance and relapse have significant effect on clinical outcome. Although tyrosine kinase inhibitors (TKIs) have dramatically improved survival of patients with chronic myelogenous leukemia (CML), TKIs have not fully cure CML due to TKI-resistant CML stem cells. Moreover, the relapse after discontinuation of TKIs has not been predicted in CML patients with best TKI-response. In our study, a model of CML stem cells derived from CML-iPSCs identified ADAM8 as an antigen of TKI-resistant CML cells. The inhibition of expression or metalloproteinase activity of ADAM8 restored TKI-sensitivity in primary samples. In addition, residual CML cells in patients with optimal TKI-response were concentrated in ADAM8+ population. Our study demonstrates that ADAM8 is a novel marker of residual CML cells even in patients with optimal TKI-response and would be a predictor of relapse and a therapeutic target of TKI-resistant CML cells.
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| Free Research Field |
血液内科学
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