Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML

被引：316

作者：

Saito, Yoriko ^{[1
]}

Uchida, Naoyuki ^{[2
]}

Tanaka, Satoshi ^{[3
]}

Suzuki, Nahoko ^{[1
]}

Tomizawa-Murasawa, Mariko ^{[1
]}

Sone, Akiko ^{[1
]}

Najima, Yuho ^{[1
]}

Takagi, Shinsuke ^{[1
,2
]}

Aoki, Yuki ^{[1
]}

Wake, Atsushi ^{[2
]}

Taniguchi, Shuichi ^{[2
]}

Shultz, Leonard D. ^{[4
]}

Ishikawa, Fumihiko ^{[1
]}

机构：

[1] RIKEN, Res Ctr Allergy & Immunol, Res Unit Human Dis Models, Yokohama, Kanagawa, Japan

[2] Toranomon Gen Hosp, Dept Hematol, Tokyo, Japan

[3] Nippon Becton Dickinson Co, Tokyo, Japan

[4] Jackson Lab, Bar Harbor, ME 04609 USA

来源：

NATURE BIOTECHNOLOGY | 2010年 / 28卷 / 03期

关键词：

ACUTE MYELOID-LEUKEMIA; COLONY-STIMULATING FACTOR; BONE-MARROW; SELF-RENEWAL; IN-VITRO; G-CSF; CHEMOTHERAPY; BLOOD; TRANSPLANTATION; MOBILIZATION;

D O I：

10.1038/nbt.1607

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Cancer stem cells have been proposed to be important for initiation, maintenance and recurrence of various malignancies, including acute myeloid leukemia (AML)(1-3). We have previously reported(4) that CD34+CD38-human primary AML stem cells residing in the endosteal region of the bone marrow are relatively chemotherapy resistant. Using a NOD/SCID/IL2r gamma(null) mouse model of human AML, we now show that the AML stem cells in the endosteal region are cell cycle quiescent and that these stem cells can be induced to enter the cell cycle by treatment with granulocyte colony-stimulating factor (G-CSF). In combination with cell cycle-dependent chemotherapy, G-CSF treatment significantly enhances induction of apoptosis and elimination of human primary AML stem cells in vivo. The combination therapy leads to significantly increased survival of secondary recipients after transplantation of leukemia cells compared with chemotherapy alone.

引用

页码：275 / U133

页数：7

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