Differentiation of mouse myeloid leukemia cells is inhibited by a factor from non-differentiating leukemia cells

Abstract

Mouse myeloid leukemia cells (MI) were induced to differentiate by a factor(s) (D‐factor) in ascitic fluid. An inhibitory activity (I‐activity) for the induction of differentiation was present in conditioned medium and lysate of MI cells resistant to the D‐factor. The I‐activity was non‐dialyzable, heat‐labile and protease‐sensitive. Most of the activity was recovered in the fraction precipitated with 30–50% saturated ammonium sulfate. The fraction inhibited induction of phagocytic activity, migrating activity and morphological changes in MI cells, which are typical properties of differentiated MI cells. Low levels of I‐activity were detected in conditioned medium or lysate of MI cells sensitive to the D‐factor. The resistant MI cells were sensitized to the D‐factor by treatment with a low concentration (5–10 ng/ml) of actinomycin D. The I‐activity in conditioned medium of actinomycin D‐treated resistant cells decreased with development of sensitivity to the D‐factor. These results suggest that production of the I‐activity in the resistant cells is closely associated with resistance of the MI cells to the D‐factor.