| RRC ID |
56159
|
| 著者 |
Miyauchi M, Koya J, Arai S, Yamazaki S, Honda A, Kataoka K, Yoshimi A, Taoka K, Kumano K, Kurokawa M.
|
| タイトル |
ADAM8 Is an Antigen of Tyrosine Kinase Inhibitor-Resistant Chronic Myeloid Leukemia Cells Identified by Patient-Derived Induced Pluripotent Stem Cells.
|
| ジャーナル |
Stem Cell Reports
|
| Abstract |
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 CML due to TKI-resistant CML stem cells. Moreover, relapse after discontinuation of TKIs has not been predicted in CML patients 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.
|
| 巻・号 |
10(3)
|
| ページ |
1115-1130
|
| 公開日 |
2018-3-13
|
| DOI |
10.1016/j.stemcr.2018.01.015
|
| PII |
S2213-6711(18)30041-9
|
| PMID |
29429960
|
| PMC |
PMC5919294
|
| MeSH |
ADAM Proteins / metabolism*
Animals
Apoptosis / drug effects
Cell Line, Tumor
Drug Resistance, Neoplasm / drug effects*
Humans
Induced Pluripotent Stem Cells / drug effects
Induced Pluripotent Stem Cells / metabolism*
K562 Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
Membrane Proteins / metabolism*
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Neoplastic Stem Cells / drug effects
Neoplastic Stem Cells / metabolism
Protein Kinase Inhibitors / pharmacology*
Protein-Tyrosine Kinases / antagonists & inhibitors*
|
| IF |
5.499
|
| 引用数 |
10
|
| リソース情報 |
| ヒト・動物細胞 |
K562(RCB0027) |
