RECONSTITUTION OF IL6-INDUCIBLE DIFFERENTIATION OF A MYELOID-LEUKEMIACELL-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 kinas e/signal transducer and activator of transcription) pathway. Defects i n this cascade are correlated with an impaired cytokine-inducible diff erentiation of various other myeloid cell lines. Although treatment wi th IL-6 increased the amount of activated transcription factor Stat3 i n the myeloid leukemia line C, differentiation was not induced. Howeve r, after cotransfection with expression constructs for the tyrosine ki nase Jak2 and Stat factors 3 or 5a, treatment of the cells with IL-6 c aused a decrease in the number of viable cells. In parallel, an increa se 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 myeloi d leukemia cells. (C) 1998 Academic Press.