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PMID: 18068630 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Loss of beta-catenin impairs the renewal of normal and CML stem cells in vivo.

Cancer cell ·Vol. 12 ·No. 6 ·2007-12-00 ·Pages 528-41

Zhao C, Blum J, Chen A, Kwon HY, Jung SH, Cook JM, Lagoo A, Reya T

Abstract

A key characteristic of stem cells and cancer cells is their ability to self-renew. To test if Wnt signaling can regulate the self-renewal of both stem cells and cancer cells in the hematopoietic system, we developed mice that lack beta-catenin in their hematopoietic cells. Here we show that beta-catenin-deficient mice can form HSCs, but that these cells are deficient in long-term growth and maintenance. Moreover, beta-catenin deletion causes a profound reduction in the ability of mice to develop BCR-ABL-induced chronic myelogenous leukemia (CML), while allowing progression of acute lymphocytic leukemia (ALL). These studies demonstrate that Wnt signaling is required for the self-renewal of normal and neoplastic stem cells in the hematopoietic system.

MeSH Terms
Animals Cell Proliferation Disease Progression Fusion Proteins, bcr-abl/metabolism Gene Deletion Genes, Reporter Hematopoietic System/pathology Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology Leukemic Infiltration Liver/pathology Lung/pathology Mice Neoplastic Stem Cells/pathology Phosphorylation Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology STAT5 Transcription Factor/metabolism Stem Cell Transplantation Wnt Proteins/metabolism beta Catenin/deficiency
Chemicals
STAT5 Transcription Factor Wnt Proteins beta Catenin Fusion Proteins, bcr-abl
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Zhao Chen
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Blum Jordan
Chen Alan
Kwon Hyog Young
Jung Seung Hye
Cook J Michael
Lagoo Anand
Reya Tannishtha
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Article Info
Journal
Cancer cell
Abbr.
Cancer Cell
ISSN
1535-6108
DOI
10.1016/j.ccr.2007.11.003
Published
2007-12-00
Pages
528-41
Language
English
Region
United States
NLM ID
101130617
PMCID
PMC2262869
Subset
IM
Grants
NIDDK NIH HHS · DK072234 · United States
NIDDK NIH HHS · R01 DK072234 · United States
NIDDK NIH HHS · R01 DK063031-02 · United States
NIAID NIH HHS · U19 AI067798-020006 · United States
NIDDK NIH HHS · R01 DK063031-05 · United States
NIAID NIH HHS · U19 AI067798 · United States
NIDDK NIH HHS · R01 DK063031 · United States
NIAID NIH HHS · U19 AI067798-030006 · United States
NIDDK NIH HHS · R01 DK063031-01S1 · United States
NIDDK NIH HHS · R01 DK063031-03 · United States
NIDDK NIH HHS · R01 DK072234-01A1 · United States
NIAID NIH HHS · AI067798 · United States
NIAID NIH HHS · U19 AI067798-010006 · United States
NIDDK NIH HHS · R01 DK063031-01 · United States
NIDDK NIH HHS · DK63031 · United States
NIDDK NIH HHS · R01 DK072234-02 · United States
NIDDK NIH HHS · R01 DK063031-04 · United States
External Links
PubMed source DOI: 10.1016/j.ccr.2007.11.003 PMC Full Text View journal details
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