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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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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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 / 薬剤耐性 / バイオマーカー / 腫瘍幹細胞 |
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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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Report
(3 results)
Research Products
(10 results)
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[Presentation] Patient-Derived Induced Pluripotent Stem Cells Revealed ADAM8/CD156 as a Novel Marker of TKI-Resistant Chronic Myeloid Leukemia Cells.2016
Author(s)
Miyauchi M, Arai S, Honda A, Yamazaki S, Kataoka K, Yoshimi A, Taoka K, Kumano K, Kurokawa M.
Organizer
American society of hematology annual meeting
Place of Presentation
San Diego, CA, USA.
Year and Date
2016-12-03
Related Report
Int'l Joint Research
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[Presentation] Pre-HPCs derived from CML-iPSCs, as a platform of CML stem cells, reveal a novel marker of TKI-resistant CML cells.2016
Author(s)
Miyauchi M, Arai S, Honda A, Yamazaki S, Kataoka K, Yoshimi A, Taoka K, Kumano K, Kurokawa M.
Organizer
日本癌学会
Place of Presentation
横浜
Year and Date
2016-10-06
Related Report
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[Presentation] Pre-hematopoietic progenitor cells (CD34+ CD43+ CD45-) derived from CML-iPSCs as powerful platform for analysis of TKI-resistant CML stem cells.2016
Author(s)
Miyauchi M, Arai S, Honda A, Yamazaki S, Kataoka K, Yoshimi A, Taoka K, Kumano K, Kurokawa M.
Organizer
International Society of Stem Cell Research
Place of Presentation
San Francisco, CA, USA.
Year and Date
2016-06-22
Related Report
Int'l Joint Research
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