The molecular control of normal and leukemic hematopoiesis: myeloid cells as a model system.

Abstract

The establishment of a cell culture system for the clonal development of hematopoietic cells has made it possible to identify the proteins that control growth and differentiation of different hematopoietic cell lineages and to discover the molecular basis of normal and abnormal cell development in blood-forming tissues. A model system with myeloid cells has shown that normal hematopoietic cells require different proteins to induce cell multiplication and cell differentiation and that a cascade of interactions between proteins determines the correct balance between immature and mature cells in normal development. Gene cloning has shown that there is a family of different genes for these proteins. Normal protein regulators of hematopoiesis can control the abnormal growth of certain types of leukemic cells and suppress malignancy by inducing differentiation to mature non-dividing cells, and there are different pathways of inducing differentiation. Results from studies on the molecular control of growth and differentiation in normal myeloid hematopoietic cells, on changes in the normal developmental program, and on the suppression of malignancy in myeloid leukemia have shown that (a) malignancy can be suppressed by inducing differentiation either with or without genetic changes in the malignant cells, (b) this suppression of malignancy does not have to restore all the normal controls, and (c) genetic abnormalities that give rise to malignancy, which include changes in homeobox genes, can be bypassed and their effects nullified by inducing differentiation that stops cells from multiplying.