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Hematopoiesis gives rise to blood cells of different lineages throughout normal life. Abnormalities in this developmental program lead to blood cell diseases including leukemia. The establishment of a cell culture system for the clonal development of hematopoieticcells made it possible to discover proteins that regulate cell viability, multiplicationand differentiationof different hematopoietic cell lineages and the molecular basis of normal and abnormal blood cell development. These regulators include cytokines now called colony stimulating factors (CSFs) and interleukins (ILs). The production of different types of hematopoietic cells with a limited lifespan, both under normal conditions and in different emergency situations such as infections, wound healing and various diseases, requires a system with considerableflexibility. A multigene family of interacting cytokines is more useful for the functions required today and for adaptation to functions that may be required in the future. than the existence of only single cytokines with high specificity where a lack of function and lack of flexibility would be lethal. A family of cytokines some of which have overlapping functions is also a useful safeguard, so that if one cytokine does not function effectively under certain conditions another can take over. A good way to obtain flexibility would be for different factors to function within a network of interactions and there is such a network of hematopoietic cytokines. This network of cytokine interactions has positive regulators such as CSFs and ILs and negative regulators such as transforming growth factor ~ (TGF-~) and tumor necrosis factor (TNF) (Fig. 1). This multigene cytokine network provides flexibility depending on which part of the network is activated and also allows amplification of response to a particular stimulus. Parts of this cytoklne network were found to function not only within the hematopoietic cell system but also in some non-hematopoietic cell types. For example, endothelial cells that make blood vessels produce interleukin-6 (IL-6) at the time of new blood vessel formation. angiogenesis, and the production of IL-6 is switched off when angiogenesis has been completed. The transient expression of IL-6 in the

The molecular control of development in normal and leukemic blood cells.