Control of growth and normal differentiation in leukemic cells: Regulation of the developmental program and restoration of the normal phenotype in myeloid leukemia

The origin and evolution of malignancy involves a sequence of genetic changes. Evidence has, however, been obtained with various types of tumors that malignant cells have not lost the genes that control normal growth and differentiation. An in vitro cloning and cell culture system has been developed to determine and dissect the controls that regulate normal myeloid cell growth, differentiation, and malignancy and to suggest a new approach to the therapy of myeloid leukemia based on the induction of normal differentiation in malignant cells. Experiments on induction of normal cell differentiation and restoration of the normal phenotype in myeloid leukemia by the physiological inducer of differentiation, the appropriate molecular form of the macrophage and granulocyte-inducing protein MGI, have also been used to formulate a general model for regulation of developmental programs and the origin and evolution of the malignancy.