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

Cancer Cell. 2007 Dec;12(6):528-41. doi: 10.1016/j.ccr.2007.11.003.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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*


  • STAT5 Transcription Factor
  • Wnt Proteins
  • beta Catenin
  • Fusion Proteins, bcr-abl