Prolongation of survival time of mice inoculated with myeloid leukemia cells by inducers of normal differentiation.

Studies were made on the effects of inducers on the leukemogenicity of sensitive mouse myeloid leukemia cells (M1) that could be induced to undergo cell differentiation into mature granulocytes and macrophages in vitro by incubation with inducers (certain proteins, bacterial lipopolysaccharides, or glucocorticoids) and of resistant M1 cells that could not be induced to differentiate into mature cells. Inducers of cell differentiation significantly enhanced the survival times of mice inoculated with sensitive cells but scarcely affected the survival times of mice inoculated with resistant cells. Some mice inoculated with the sensitive cells and treated with lipopolysaccharide did not develop leukemia. The sensitive and resistant clone cells contained similar common tumor-related surface antigens. Treatment with lipopolysaccharide was also effective in athymic nude mice inoculated with the sensitive M1 cells. Lipopolysaccharide or glucocorticoid significantly stimulated differentiation of the sensitive cells cultured in a diffusion chamber in vivo but had little effect on differentiation of resistant cells. These results suggest the possibility of treating, with partial success, leukemia in vivo with differentiation inducers.