期刊
STEM CELL REPORTS
卷 10, 期 3, 页码 1115-1130出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2018.01.015
关键词
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资金
- Advanced Research & Development Programs for Medical Innovation (AMED-CREST)
- Japan Society for the Promotion of Science (JSPS) KAKENHI [14J02953, 16K19568]
- Foundation for Promotion of Cancer Research
- Okinaka Memorial Institute for Medical Research
- Tokyo Biochemical Research Foundation
- Astellas
- Bristol-Myers Squibb
- Novartis
- Pfizer
- Takeda
- Grants-in-Aid for Scientific Research [16H01196, 16K19568, 14J02953] Funding Source: KAKEN
Properties of cancer stem cells involved in drug resistance and relapse have significant effects on clinical outcome. Although tyrosine kinase inhibitors (TKIs) have dramatically improved survival of patients with chronic myeloid leukemia (CML), TKIs have not fully cured CMLdue to TKI-resistantCMLstem cells. Moreover, relapse after discontinuation of TKIs has not been predicted inCMLpatients with the best TKI response. In our study, a model of CML stem cells derived from CML induced pluripotent stem cells 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 the ADAM8+ population. Our study demonstrates that ADAM8 is a 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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