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

Jenny Yeung; Maria Teresa Esposito; Arnaud Gandillet; Bernd B. Zeisig; Emmanuel Griessinger; Dominique Bonnet; Chi Wai Eric So

doi:10.1016/j.ccr.2010.10.032

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

Jenny Yeung, Maria Teresa Esposito, Arnaud Gandillet, Bernd B. Zeisig, Emmanuel Griessinger, Dominique Bonnet, Chi Wai Eric So

Research output: Contribution to journal › Article › peer-review

243 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	606 - 618
Number of pages	13
Journal	CANCER CELL
Volume	18
Issue number	6
DOIs	https://doi.org/10.1016/j.ccr.2010.10.032
Publication status	Published - 14 Dec 2010

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title = "β-Catenin Mediates the Establishment and Drug Resistance of MLL Leukemic Stem Cells",

abstract = "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.",

author = "Jenny Yeung and Esposito, {Maria Teresa} and Arnaud Gandillet and Zeisig, {Bernd B.} and Emmanuel Griessinger and Dominique Bonnet and So, {Chi Wai Eric}",

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T1 - β-Catenin Mediates the Establishment and Drug Resistance of MLL Leukemic Stem Cells

AU - Yeung, Jenny

AU - Esposito, Maria Teresa

AU - Gandillet, Arnaud

AU - Zeisig, Bernd B.

AU - Griessinger, Emmanuel

AU - Bonnet, Dominique

AU - So, Chi Wai Eric

PY - 2010/12/14

Y1 - 2010/12/14

N2 - 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.

AB - 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.

U2 - 10.1016/j.ccr.2010.10.032

DO - 10.1016/j.ccr.2010.10.032

M3 - Article

VL - 18

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JO - CANCER CELL

JF - CANCER CELL

IS - 6

ER -

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

Abstract

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