Cancer Cell
Volume 18, Issue 6, 14 December 2010, Pages 606-618
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Article
β-Catenin Mediates the Establishment and Drug Resistance of MLL Leukemic Stem Cells

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Summary

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 β-catenin was activated during development of MLL leukemic stem cells (LSCs). Suppression of β-catenin reversed LSCs to a pre-LSC-like stage and significantly reduced the growth of human MLL leukemic cells. Conditional deletion of β-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 β-catenin expression. These results unveil previously unrecognized multifaceted functions of β-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.

Highlights

► Differential activation of Wnt/β-catenin pathway is required for MLL LSC development ► Suppression of β-catenin reverses MLL LSCs to a pre-LSC like stage ► Down modulation of β-catenin impedes human AML proliferation ► Suppression of β-catenin sensitizes MLL LSCs to GSK3 inhibitors

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