PTEN is a tumor suppressor in CML stem cells and BCR-ABL-induced leukemias in mice

Blood. 2010 Jan 21;115(3):626-35. doi: 10.1182/blood-2009-06-228130. Epub 2009 Nov 18.


The tumor suppressor gene phosphatase and tensin homolog (PTEN) is inactivated in many human cancers. However, it is unknown whether PTEN functions as a tumor suppressor in human Philadelphia chromosome-positive leukemia that includes chronic myeloid leukemia (CML) and B-cell acute lymphoblastic leukemia (B-ALL) and is induced by the BCR-ABL oncogene. By using our mouse model of BCR-ABL-induced leukemias, we show that Pten is down-regulated by BCR-ABL in leukemia stem cells in CML and that PTEN deletion causes acceleration of CML development. In addition, overexpression of PTEN delays the development of CML and B-ALL and prolongs survival of leukemia mice. PTEN suppresses leukemia stem cells and induces cell-cycle arrest of leukemia cells. Moreover, PTEN suppresses B-ALL development through regulating its downstream gene Akt1. These results demonstrate a critical role of PTEN in BCR-ABL-induced leukemias and suggest a potential strategy for the treatment of Philadelphia chromosome-positive leukemia.

Publication types

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

MeSH terms

  • Animals
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cells, Cultured
  • Disease Progression
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / physiology
  • Gene Expression Regulation, Leukemic / physiology
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • PTEN Phosphohydrolase / physiology*
  • Survival Analysis
  • Transplantation, Heterologous
  • Tumor Suppressor Proteins* / genetics
  • Tumor Suppressor Proteins* / metabolism
  • Tumor Suppressor Proteins* / physiology
  • Up-Regulation / physiology


  • Tumor Suppressor Proteins
  • Fusion Proteins, bcr-abl
  • PTEN Phosphohydrolase
  • Pten protein, mouse