SUPPRESSION OF THE DEVELOPMENT OF MURINE MYELOID-LEUKEMIA WITH GRANULOCYTE-COLONY-STIMULATING FACTOR BY INDUCING APOPTOSIS OF LEUKEMIC-CELLS

We studied the antileukemic effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) by using a radiation-induced murine myeloid leukemia cell line C2M-A5. Intravenous inoculation of C2M-A5 cells into C3H/He mice resulted in the development of myeloid leukemia. However, the leukemic death of the mice was completely suppressed by the subcutaneous injections of rhG-CSF. In order to clarify the mechanism of the suppression, effects of rhG-CSF on C2M-A5 cells were studied in vitro. While C2M-A5 cells grew exponentially in the absence of rhG-CSF, the viability, the growth, and the self-renewal capacity of C2M-A5 cells were all suppressed in cultures in the presence of rhG-CSF. Preincubation with rhc-CSF for 48 h deprived C2M-A5 cells of the ability to induce leukemia in syngeneic mice. Morphological examination revealed the appearance of apoptotic changes of C2M-A5 cells in cultures containing rhG-CSF over the P-day incubation period. In gel electrophoresis, the DNA from C2M-A5 cells incubated with rhG-CSF for 48 h showed a ladder of degradated DNA bands compatible with apoptosis. From these results, we concluded that the apoptosis of C2M-A5 cells played a key role in the anti-leukemic effect of rhG-CSF.