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 eventual ly progressing to blast crisis, which resembles human chronic myeloid leuke mia. Similarly, mice reconstituted with ES cell-derived junB(-/-) fetal liv er cells also develop a myeloproliferative disease. In both cases, the abse nce of JunB expression results in increased numbers of granulocyte progenit ors, which display enhanced GM-CSF-mediated proliferation and extended surv ival, associated with changes in the expression levels of the GM-CSF alpha receptor, the anti-apoptotic proteins Bcl2 and Bclx, and the cell cycle reg ulators p16(INK4a) and c-Jun. Importantly, ectopic expression of JunB fully reverts the immature and hyperproliferative phenotype of JunB-deficient my eloid cells. These results identify JunB as a key transcriptional regulator of myelopoiesis and a potential tumor suppressor gene.