B-myb alters the response of myeloid precursor cells to G-CSF

Abstract

The human B-myb gene encodes a cell cycle-regulated DNA-binding phosphoprotein which functions as a transcription factor with an important role in cell cycle progression, survival, and differentiation. Recently, it has been demonstrated that ectopic murine B-myb expression blocked the ability of 32Dcl3 cells to proliferate in response to granulocyte colony-stimulating factor (G-CSF) and accelerated the induction of terminal differentiation. In contrast, we report that while 32Dcl3 cells overexpressing human B-myb do display some markers of myeloid differentiation earlier than parental cells, including the expression of myeloperoxidase mRNA and the appearance of band myelocytes in G-CSF-induced cultures, the induction of late markers of differentiation is inhibited. The expression of lactoferrin mRNA is absent and the appearance of terminally differentiated polymorphonuclear cells is severely impaired in B-myb-expressing 32Dcl3 cells. Furthermore, continuous exposure to G-CSF results in the outgrowth of a culture which expresses increased levels of B-myb RNA and is dependent on G-CSF for proliferation while retaining responsiveness to interleukin-3. These data suggest that the B-myb gene is involved in early transcriptional events during myeloid differentiation, but that its expression prevents terminal differentiation.