title: Chronic myeloid leukemia with increased granulocyte progenitors in mice lacking junB expression in the myeloid lineage.
abstract: 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.
authors.affiliation: Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Passegué
authors.forename: W
authors.initials: W
authors.lastname: Jochum
authors.forename: M
authors.initials: M
authors.lastname: Schorpp-Kistner
authors.forename: U
authors.initials: U
authors.lastname: Möhle-Steinlein
authors.forename: E F
authors.initials: EF
authors.lastname: Wagner
mesh_terms: 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
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D016178:Granulocyte-Macrophage Colony-Stimulating Factor