Macrophage colony-stimulating factor stimulates growth progression of the G1-phase fraction and induces monocytic differentiation of the G2/M-phase fraction in human myeloid leukemia cells.

The human myeloid leukemia cell line (NKM-1) proliferates in response to exogenous macrophage colony-stimulating factor (M-CSF) in serum-free medium. This CSF alone, however, does not induce any feature of cell differentiation in NKM-1 cells. We showed that terminal monocytic differentiation is partially observed only when NKM-1 cells are sequentially treated with 1,25-dihydroxyvitamin D3 and M-CSF, as evaluated by cell morphology, analysis of surface antigens, and phagocytic function. To determine whether there might be an association between the actions of M-CSF and special phases of the cell cycle, we separated D3-treated cells into cycle-specific fractions by centrifugal elutriation. G1-enriched cells were mostly stimulated for growth progression with M-CSF. On the other hand, G2/M-enriched cells were significantly induced into monocytic differentiation. The cell percentage in the G2/M phase has clearly correlated with that of terminally differentiated cells by M-CSF. These results suggest that two distinct actions of M-CSF to stimulate cell proliferation and differentiation could work on different phases of the cell cycle: cell growth in the G1 phase and cell differentiation in the G2/M phase.