The Wellcome Foundation Lecture, 1986 - The molecular regulators of normal and leukaemic blood cells
- 21 August 1987
- journal article
- research article
- Published by The Royal Society in Proceedings of the Royal Society of London. B. Biological Sciences
- Vol. 231 (1264) , 289-312
- https://doi.org/10.1098/rspb.1987.0045
Abstract
The development of a cell-culture system for the cloning and clonal differentiation of different types of blood cell has made it possible to identify: (i), the proteins that regulate growth and differentiation of different cell lineages in normal and leukaemic blood cells; (ii), the molecular basis of normal and abnormal control of cell development in blood-forming tissue; and (iii), how to suppress malignancy in leukaemic cells. By using myeloid blood cells as a model system, it has been shown that normal blood cells require different proteins to induce cell viability and multiplication (growth-inducers) and differentiation (differentiation-inducers), that there is a hierarchy of growth-inducers which act at various stages of cell development, and that a growth-inducer can switch on production of a differentiation inducer. Gene cloning has established a multigene family for these proteins. Identification of these proteins and their interaction has shown how growth and differentiation are regulated in normal develpment and the mechanisms that uncouple growth and differentiation so as to produce malignant cells. Normal cells require an external source of growth-inducing protein for cell viability and multiplication. Cells can become leukaemic by genetically changing this normal requirement for growth without blocking response to normal differentiation-inducers. The mature cells induced by adding these normal protein-inducers are then no longer malignant. Other genetic changes which inhibit differentiation by the normal blood-cell regulatory proteins can occur in the evolution of leukaemia. But even these leukaemic cells may still be induced to differentiate by other compounds that can induce differentiation by alternative pathways. The differentiation of leukaemic to mature cells, which stops the cells from multiplying, results in the suppression of malignancy by by-passing genetic changes that produce the malignant phenotype. The activity of blood-cell growth- and differentiation-inducing proteins has been shown in culture and in the body. They can, therefore, be clinically useful to correct defects in the development of normal and leukaemic blood cells.This publication has 115 references indexed in Scilit:
- The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF 1Cell, 1985
- Control of in vivo differentiation of myeloid leukemic cells. iv. inhibition of leukemia development by myeloid differentiation‐inducing proteinInternational Journal of Cancer, 1984
- Potential pre‐screening for therapeutic agents that induce differentiation in human myeloid leukemia cellsInternational Journal of Cancer, 1980
- Genetic dissociation of different cellular effects of interferon on myeloid leukemic cellsInternational Journal of Cancer, 1978
- Chromosome balance and the control of malignancyJournal of Cellular Physiology, 1976
- Control of normal differentiation of myeloid leukemic cells. V. Normal differentiation in aneuploid leukemic cells and the chromosome banding pattern of D+ and D− clonesInternational Journal of Cancer, 1974
- Chromosomal Control of Reversion in Transformed CellsNature, 1971
- Control of the Reversion of Properties in Transformed CellsNature, 1970
- Reversion of Properties in Cells transformed by Polyoma VirusNature, 1968
- In Vitro Cell Transformation by X-IrradiationNature, 1966