Regulation of Growth and Differentiation in Normal and Leukemic Hematopoiesis
Our establishment of a cell culture system for the clonal development of hematopoietic cells made it possible to identify the proteins that regulate 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 different 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 nondividing cells. Genetic abnormalities that give rise to malignancy in these leukemic cells can be bypassed and their effects nullified by inducing differentiation which stops cells from multiplying. These hematopoietic regulatory proteins are active in culture and in vivo, and they can be used clinically to correct defects in blood cell development. The results provide new possibilities for therapy.