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ファイル
言語
日本語
著者
内容記述(抄録等)
The treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKIs) has substantially extended patient survival. However, TKIs do not effectively eliminate CML stem cells. In fact, CML stem cells persist and cause relapse in the majority of patients upon discontinuation of the drug treatment. Transcriptomic and proteomic analyses have revealed that p53 and c-Myc play defining roles in CML stem cell survival, suggesting that the dual targeting of p53 and c-Myc may selectively eliminate stem cells in patients with CML. Since the downregulation of c-Myc and then upregulation of p21 (a target gene of p53) are commonly observed during the differentiation of acute myeloid leukemia cells induced by differentiation inducers, we hypothesized that differentiation-inducing agents may be useful in regulating c-Myc and p53 expression in CML cells. In the present study, we demonstrate that some differentiation-inducing agents effectively suppress the self-renewal ability of CML cells, and that the combination of these inducers with TKIs results in significantly greater inhibitory effects on CML cell growth compared to the use of TKIs or the inducer alone. The KU812 cells were treated with various concentrations of the inducers in the presence or absence of 30 nM imatinib for 4 days. Among the differentiation inducers we tested, cotylenin A (CN-A) was the most potent at inhibiting the self-renewal ability of the CML cells. CN-A induced the robust expression of CD38, a marker of committed progenitor and more differentiated myelomonocytic cells, and rapidly suppressed c-Myc expression and upregulated p21 expression in CML cells. Thus, these results suggest that CN-A may have potential to promote the elimination of stem cells in CML.
掲載誌名
INTERNATIONAL JOURNAL OF ONCOLOGY
52
開始ページ
2061
終了ページ
2068
ISSN
1019-6439
発行日
20180421
DOI
出版者
Spandidos Publications
資料タイプ
学術雑誌論文
ファイル形式
PDF
著者版/出版社版
出版社版
部局
医学部
学位授与番号
甲第655号
学位授与年月日
2019-03-22
学位名
博士(医学)
学位授与機関
島根大学
学位論文研究科コード
医学系研究科
学位授与年度
2018
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