Transcription factors that regulate growth and differentiation of myeloid cells

Abstract

Recently much progress has been made in our understanding of how myeloid progenitor cells undergo commitment and become mature granulocytes or monocytes/macrophages. Studies of normal and leukemic myeloid cells as well as those of cells derived from mice with targeted disruption showed that a series of transcription factors play a major role in both commitment and maturation of myeloid cells. This is primarily because these transcription factors direct an ordered pattern of gene expression according to a well-defined developmental program. PU.1, an Ets family member, is one of the master transcription factors identified to regulate development of both granulocytes and monocytes/macrophages. Further, C/EBPalpha and C/EBPvarepsilon of the bZip family have important roles in directing granulocytic maturation. A number of additional transcription factors such as AML1, RARalpha, MZF-1, Hox and STAT families of transcription factors, Egr-1 and c-myb etc are shown to play roles in myeloid cell differentiation. Our laboratory has recently obtained evidence that ICSBP, a member of the IRF family, is involved in lineage commitment during myeloid cell differentiation and stimulates maturation of functional macrophages. Future elucidation of pathways and networks through which these transcription factors act in various stages of development would provide a more definitive picture of myeloid cell commitment and maturation.