Ablation of Fbxw7 Eliminates Leukemia-Initiating Cells by Preventing Quiescence

被引：137

作者：

Takeishi, Shoichiro ^{[1
,2
]}

Matsumoto, Akinobu ^{[1
,2
]}

Onoyama, Ichiro ^{[1
,2
]}

Naka, Kazuhito ^{[3
]}

Hirao, Atsushi ^{[2
,3
]}

Nakayama, Keiichi I. ^{[1
,2
]}

机构：

[1] Kyushu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Higashi Ku, Fukuoka 8128582, Japan

[2] Japan Sci & Technol Agcy, CREST Core Res Evolut Sci & Technol, Kawaguchi, Saitama 3320012, Japan

[3] Kanazawa Univ, Canc Res Inst, Ctr Canc & Stem Cell Res, Div Mol Genet, Kanazawa, Ishikawa 9201192, Japan

来源：

CANCER CELL | 2013年 / 23卷 / 03期

关键词：

CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; MYELOPROLIFERATIVE DISEASE; CANCER-THERAPY; BONE-MARROW; IN-VIVO; IMATINIB; MICE; CML;

D O I：

10.1016/j.ccr.2013.01.026

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：347 / 361

页数：15

共 34 条

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