The B-myb gene encodes a nuclear DNA binding phosphoprotein which shares considerable homology with the c-myb protooncogene through their DNA binding domains. While expression of the c-myb gene is largely limited to immature hematopoietic cells, B-myb is expressed in a wide variety of lineages, including immature hematopoietic cells. Expression of both genes is required for hematopoietic cell proliferation. Constitutive expression of the c-myb gene blocks the differentiation of hematopoietic cells, and constitutive expression of the B-myb gene blocks the differentiation of neuronal cells. To determine the role of B-myb in hematopoietic differentiation, the effects of in appropriate B-myb expression were examined in the same cell lines used to study the role of c-myb in hematopoietic cells. B-myb expression from a zinc-inducible expression vector resulted in the inhibition of DMSO-induced differentiation of MEL cells when zinc was added to the culture medium 48 hours after DMSO. While constitutive B-myb expression did not confer a proliferative advantage to the IL-3 dependent myeloid precursor 32D c13 cell line, it did cause a delay in apoptosis induced in these cells by growth factor withdrawal. Constitutive B-myb expression induced the expression of myeloperoxidase, an early marker of myeloid differentiation, in proliferating 32D c13 cells. The induction of differentiation by granulocyte-colony stimulating factor (G-CSF) was blocked in B-myb transfectants, which do not express the late differentiation marker, lactoferrin, and which fail to upregulate expression of the G-CSF receptor, an immediate-early response to G-CSF stimulation. Furthermore, constitutive B-myb expression altered the response of 32D c13 cells to G-CSF, in that they proliferated indefinitely, rather than terminally differentiated, in its presence.
