Chronic myeloid leukemia with increased granulocyte progenitors in mice lacking junB expression in the myeloid lineage

Cell. 2001 Jan 12;104(1):21-32. doi: 10.1016/s0092-8674(01)00188-x.


The functions of JunB during myelopoiesis were studied in vivo. Transgenic mice specifically lacking JunB expression in the myeloid lineage (junB(-/-)Ubi-junB mice) develop a transplantable myeloproliferative disease eventually progressing to blast crisis, which resembles human chronic myeloid leukemia. Similarly, mice reconstituted with ES cell-derived junB-/- fetal liver cells also develop a myeloproliferative disease. In both cases, the absence of JunB expression results in increased numbers of granulocyte progenitors, which display enhanced GM-CSF-mediated proliferation and extended survival, associated with changes in the expression levels of the GM-CSFalpha receptor, the anti-apoptotic proteins Bcl2 and Bclx, and the cell cycle regulators p16(INK4a) and c-Jun. Importantly, ectopic expression of JunB fully reverts the immature and hyperproliferative phenotype of JunB-deficient myeloid cells. These results identify JunB as a key transcriptional regulator of myelopoiesis and a potential tumor suppressor gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Cell Division / drug effects
  • Cell Division / immunology
  • Cell Lineage / immunology
  • Gene Expression / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Granulocytes / cytology*
  • In Vitro Techniques
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / physiopathology*
  • Leukopoiesis / immunology
  • Mice
  • Mice, Knockout
  • Phenotype
  • Proto-Oncogene Proteins c-jun / genetics*
  • Stem Cells / cytology*
  • Transgenes / immunology


  • Proto-Oncogene Proteins c-jun
  • Granulocyte-Macrophage Colony-Stimulating Factor