Eclectic mechanisms of heme regulation of hematopoiesis

Regulatory features of heme (ferroprotoporphyrin IX) on hematopoietic growth/differentiation and related processes are reviewed. It is emphasized that expressions of specific erythroid and nonerythroid heme biosynthetic and degradatory enzymes are required, and the regulatory processes whereby this occurs is considered. The specificity of heme, relationship to cellular events such as differentiation, response to growth factors, oncogene and receptor expression, and how heme counteracts toxic effects such as viral growth are all discussed. The significance of heme in the hemopoietic bone marrow microenvironment and growth factor network are considered. Finally, the third pathway for arachidonic acid metabolism via the heme-cytochrome P450 monooxygenase system, in addition to cyclooxygenase and lipoxygenase, by bone marrow adherent cells and its role in cellular differentiation is briefly reviewed.