Loss of beta-catenin impairs the renewal of normal and CML stem cells in vivo.
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.
Zhao
Chen
C
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Blum
Jordan
J
Chen
Alan
A
Kwon
Hyog Young
HY
Jung
Seung Hye
SH
Cook
J Michael
JM
Lagoo
Anand
A
Reya
Tannishtha
T
D000818:Animals; D049109:Cell Proliferation; D018450:Disease Progression; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D017353:Gene Deletion; D017930:Genes, Reporter; D006413:Hematopoietic System / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D017254:Leukemic Infiltration; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D051379:Mice; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010766:Phosphorylation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology; D050799:STAT5 Transcription Factor / Q000378:metabolism; D033581:Stem Cell Transplantation; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000172:deficiency*
D050799:STAT5 Transcription Factor; D051153:Wnt Proteins; D051176:beta Catenin; D016044:Fusion Proteins, bcr-abl