Hematopoietic regulators: redundancy or subtlety?

EMATOPOIESIS requires a highly complex series of H cellular events in which a small population of stem cells needs to generate continuously large populations of maturing cells in eight major lineages. Normally, the diverse proliferative, differentiative, and maturation events required to achieve this occur with precision, which leads to the expectation that the regulatory mechanisms involved would need to be complex. It can also be anticipated that the entry of mature cells into the circulation, their selective localization in appropriate tissues, and their functional activation are also events requiring sophisticated regulatory control. Given the likely complexity of these events and the knowledge that much of this regulation is achieved by the use of regulatory molecules that can be humoral or cell-associated, it is not surprising that many such regulatory molecules have been Characterized, purified, and produced in recombinant form. The known regulators with proliferative effects on one or other hematopoietic population already exceed 20 in number and to these need to be added a variety of inhibitory factors and a number of factors allowing selective cell-cell adhesion. Many additional candidate factors are in the early phase of characterization. This degree of complexity in biologic processes is familiar enough to those who have addressed the details of coagulation or complement activation. However, for some of those working with the proliferative hematopoietic regulatory factors, there are aspects of the regulators so far characterized that have a raised a growing conviction that these regulators may exhibit a high degree of redundancy. In short, there appear to be more regulators with similar or overlapping actions than would seem to be really necessary to achieve the required cell proliferation.