THE MOLECULAR CONTROL OF HEMATOPOIESIS AND LEUKEMIA (REPRINTED FROM -SCIENCES-PARIS,-SCIENCES-DE-LA-VIE-LIFE-SCIENCES, VOL 316, 1993, PG 882-896)

The establishment of a cell culture system for the clonal development of haemopoietic cells made it possible to discover the proteins that r egulate cell viability, growth and differentiation of different haemop oietic cell lineages and the molecular basis of normal and abnormal de velopment in blood-forming tissues. These regulators include cytokines now called colony stimulating factors (CSFs) and interleukins (ILs). Different cytokines can induce cell viability, multiplication and diff erentiation, and haemopoiesis is controlled by a network of cytokine i nteractions. The multigene network includes positive regulators such a s CSFs and ILs and negative regulators such as transforming growth fac tor p and tumour necrosis factor. The cytokine network which has arise n during evolution allows considerable flexibility depending on which part of the network is activated and the ready amplification of respon se to a particular stimulus. The CSFs and ILs induce cell viability by inhibiting programmed cell death (apoptosis). Programmed cell death i s also regulated by the genes wild-type and mutant p 53, c-myc and bcl -2, and suppression or induction of this programme can result in tumou r promotion or tumour suppression. Cytokines that regulate normal haem opoiesis can control the abnormal growth of certain types of leukaemic cells and suppress malignancy by inducing differentiation. Genetic ab normalities that give rise to malignancy in these leukaemic cells can be by-passed and their effects nullified by inducing differentiation a nd programmed cell death. The haemopoietic cytokines discovered in cul ture are active in vivo and are being used clinically to correct defec ts in haemopoiesis.