Wnt pathway contributes to the protection by bone marrow stromal cells of acute lymphoblastic leukemia cells and is a potential therapeutic target

Cancer Lett. 2013 Jun 1;333(1):9-17. doi: 10.1016/j.canlet.2012.11.056. Epub 2013 Jan 16.


Leukemia cells are protected by various components of their microenvironment, including marrow stromal cells (MSCs). To understand the molecular mechanisms underlying this protection, we cultured acute lymphoblastic leukemia (ALL) cells with MSCs and studied the effect of the latter on the molecular profiling of ALL cells at the mRNA and protein levels. Our results indicated that activated Wnt signaling in ALL cells is involved in MSC-mediated drug resistance. Blocking the Wnt pathway sensitized the leukemia cells to chemotherapy and improved overall survival in a mouse model. Targeting the Wnt pathway may be an innovative approach to the treatment of ALL.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Cycle
  • Cytarabine / pharmacology
  • Gene Expression Regulation, Leukemic
  • Heterocyclic Compounds, 3-Ring / pharmacology
  • Humans
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Mice, SCID
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Wnt Signaling Pathway / physiology*
  • beta Catenin / physiology


  • CTNNB1 protein, human
  • Heterocyclic Compounds, 3-Ring
  • XAV939
  • beta Catenin
  • Cytarabine