The molecular control of hematopoiesis: from clonal development in culture to therapy in the clinic.

Abstract

The establishment of a cell culture system for the clonal development of hematopoietic cells has made it possible to discover the proteins that regulate cell viability, growth and differentiation of different hematopoietic cell lineages and the molecular basis of normal and abnormal cell development in blood-forming tissues. These regulators include cytokines now called colony stimulating factors and interleukins. Different cytokines can induce cell viability, multiplication and differentiation, and hematopoiesis is controlled by a network of interactions between these cytokines. This network includes positive regulators such as colony stimulating factors and interleukins and negative regulators such as transforming growth factor beta and tumor necrosis factor. Gene cloning has shown that there is a family of different genes for these cytokines. The functioning of the network requires an appropriate balance between positive and negative regulators and the selective regulation of programmed cell death (apoptosis). There are different ways of inducing or inhibiting programmed cell death, and differences in the regulation of this program can result in tumor promotion or tumor suppression. The cytokine network which has arisen during evolution allows considerable flexibility, depending on which part of the network is activated and the ready amplification of response to a particular stimulus. A network may also be necessary to stabilize the whole system. Cytokines that regulate hematopoiesis can induce the expression of genes for transcription factors can thus ensure the autoregulation and transregulation of cytokine genes that occur in the network.(ABSTRACT TRUNCATED AT 250 WORDS)