Mechanisms controlling the kinetics in proliferation and differentiation of populations of mouse myeloid leukemic cells in vitro.

The kinetics of differentiation and proliferation of clone cells (B24) of mouse myeloid leukemic M1 cells in vitro were studied by quantitative determination of cellular morphology. B24 cells were induced to differentiate into only macrophagelike cells by an inducer of differentiation in conditioned medium (CM) of embryo cells. During cell differentiation, the ratio of the area of the nucleus to that of the cell (N.C.R.) decreased from about 55% to 10%. Decrease in the N.C.R. was used as an index of cell differentiation in analysis of the kinetics of differentiation of cells treated with various concentrations of CM. The results showed that the process of differentiation was promoted by increasing the concentration of CM, and that the transition of the cells from the undifferentiated state to the differentiated state occurred in a stochastic manner. Comparison of these morphometric results with those of autoradiography showed that the labeling index of the cells decreases gradually in association with decrease in the N.C.R. of the cells from 50% to 30%. A stochastic model for the kinetics of proliferation and differentiation of the cells simulated the experimental observations on the production of differentiated cells.