β-Catenin Mediates the Establishment and Drug Resistance of MLL Leukemic Stem Cells

被引：237

作者：

Yeung, Jenny ^{[1
]}

Esposito, Maria Teresa ^{[1
]}

Gandillet, Arnaud ^{[2
]}

Zeisig, Bernd B. ^{[1
]}

Griessinger, Emmanuel ^{[2
]}

Bonnet, Dominique ^{[2
]}

So, Chi Wai Eric ^{[1
,3
]}

机构：

[1] Kings Coll London, Dept Haematol Med, Leukaemia & Stem Cell Biol Grp, London SE5 9NU, England

[2] London Res Inst, Canc Res UK Haematopoiet Stem Cell Grp, London WC2A 3PX, England

[3] Inst Canc Res, Haematooncol Sect, Sutton SM2 5NG, Surrey, England

来源：

CANCER CELL | 2010年 / 18卷 / 06期

关键词：

ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC STEM; LONG-TERM; CANCER; MURINE; MAINTENANCE; MODEL; IDENTIFICATION; TRANSFORMATION; METHYLATION;

D O I：

10.1016/j.ccr.2010.10.032

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Identification of molecular pathways essential for cancer stem cells is critical for understanding the underlying biology and designing effective cancer therapeutics. Here, we demonstrated that beta-catenin was activated during development of MLL leukemic stem cells (LSCs). Suppression of beta-catenin reversed LSCs to a pre-LSC-like stage and significantly reduced the growth of human MLL leukemic cells. Conditional deletion of beta-catenin completely abolished the oncogenic potential of MLL-transformed cells. In addition, established MLL LSCs that have acquired resistance against GSK3 inhibitors could be resensitized by suppression of beta-catenin expression. These results unveil previously unrecognized multifaceted functions of beta-catenin in the establishment and drug-resistant properties of MLL stem cells, highlighting it as a potential therapeutic target for an important subset of AMLs.

引用

页码：606 / 618

页数：13

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