Chronic myeloid leukemia with increased granulocyte progenitors in mice lacking junB expression in the myeloid lineage.
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.
Passegué
E
E
Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Jochum
W
W
Schorpp-Kistner
M
M
Möhle-Steinlein
U
U
Wagner
E F
EF
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology*; D066298:In Vitro Techniques; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D019891:Leukopoiesis / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology*; D019076:Transgenes / Q000276:immunology
D016755:Proto-Oncogene Proteins c-jun; D016178:Granulocyte-Macrophage Colony-Stimulating Factor