Reconstitution of IL6-inducible differentiation of a myeloid leukemia cell line by activated Stat factors

Differentiation of the myeloid leukemia cell line M1 by treatment with IL6-type cytokines depends on activation of the Jak/Stat (Janus kinase/signal transducer and activator of transcription) pathway. Defects in this cascade are correlated with an impaired cytokine-inducible differentiation of various other myeloid cell lines. Although treatment with IL-6 increased the amount of activated transcription factor Stat3 in the myeloid leukemia line C, differentiation was not induced. However, after cotransfection with expression constructs for the tyrosine kinase Jak2 and Stat factors 3 or 5a, treatment of the cells with IL-6 caused a decrease in the number of viable cells. In parallel, an increase in the percentage of differentiated cells occurred. These findings are consistent with the hypothesis that the Jak/Stat signaling cascade plays an important role in cytokine-induced differentiation of myeloid leukemia cells. (C) 1998 Academic Press.