B-myb alters the response of myeloid precursor cells to G-CSF.
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.
Engelhard
A
A
Department of Microbiology and Immunology, Kimmel Cancer Institute, Philadelphia, Pennsylvania, 19107, USA.
Campbell
K
K
Calabretta
B
B
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051379:Mice; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis; D000099232:Proto-Oncogene Protein Spi-1
D022762:CCAAT-Enhancer-Binding Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016179:Granulocyte Colony-Stimulating Factor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C083058:C-EPB transcription factor; C064352:MYBL2 protein, human; C499306:Mybl2 protein, mouse