| RRC ID |
68726
|
| 著者 |
Takeishi S, Matsumoto A, Onoyama I, Naka K, Hirao A, Nakayama KI.
|
| タイトル |
Ablation of Fbxw7 eliminates leukemia-initiating cells by preventing quiescence.
|
| ジャーナル |
Cancer Cell
|
| Abstract |
Imatinib eradicates dividing progenitor cells of chronic myeloid leukemia (CML) but does not effectively target nondividing leukemia-initiating cells (LICs); thus, the disease often relapse after its discontinuation. We now show that Fbxw7 plays a pivotal role in maintenance of quiescence in LICs of CML by reducing the level of c-Myc. Abrogation of quiescence in LICs by Fbxw7 ablation increased their sensitivity to imatinib, and the combination of Fbxw7 ablation with imatinib treatment resulted in a greater depletion of LICs than of normal hematopoietic stem cells in mice. Purging of LICs by targeting Fbxw7 to interrupt their quiescence and subsequent treatment with imatinib may thus provide the basis for a promising therapeutic approach to CML.
|
| 巻・号 |
23(3)
|
| ページ |
347-61
|
| 公開日 |
2013-3-18
|
| DOI |
10.1016/j.ccr.2013.01.026
|
| PII |
S1535-6108(13)00045-7
|
| PMID |
23518349
|
| MeSH |
Animals
Apoptosis
Benzamides / therapeutic use*
Cell Cycle
Down-Regulation
F-Box Proteins / antagonists & inhibitors*
F-Box Proteins / genetics
F-Box Proteins / metabolism*
F-Box-WD Repeat-Containing Protein 7
Hematopoietic Stem Cells / physiology
Imatinib Mesylate
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neoplastic Stem Cells / physiology
Piperazines / therapeutic use*
Protein Kinase Inhibitors / therapeutic use
Proto-Oncogene Proteins c-myc / metabolism*
Pyrimidines / therapeutic use*
RNA Interference
RNA, Small Interfering
Tumor Suppressor Protein p53 / metabolism
Ubiquitin-Protein Ligases / antagonists & inhibitors*
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / metabolism*
|
| IF |
26.602
|
| リソース情報 |
| ヒト・動物細胞 |
OP9(RCB1124) |
