Myeloblastin is a granulocyte colony-stimulating factor-responsive gene conferring factor-independent growth to hematopoietic cells

Hematopoiesis depends on a pool of quiescent hematopoietic stem/progenitor cells. When exposed to specific cytokines, a portion of these cells enters the cell cycle to generate an amplified progeny. Myeloblastin (MBN) initial ly was described as involved in proliferation of human leukemia cells. The granulocyte colony-stimulating factor (G-CSF), which stimulates the prolife ration of granulocytic precursors, up-regulates MBN expression. Here we sho w that constitutive overexpression of MBN confers factor-independent growth to murine bone marrow-derived Ba/F3/G-CSFR cells. Our results point to MBN as a C-CSF responsive gene critical to factor-independent growth and indic ate that expression of the G-CSF receptor is a prerequisite to this process . A 91-bp MBN promoter region containing PU.1, C/EBP, and c-Myb binding sit es is responsive to G-CSF treatment. Although PU.1. C/EBP, and c-Myb transc ription factors all were critical for expression of MEN, its up-regulation by G-CSF was associated mainly with PU.1. These findings suggest that MBN i s an important target of PU.1 and a key protease for factor-independent gro wth of hematopoietic cells.