MODULATION OF THE ACTIVATION STATUS OF STAT5A DURING LIF-INDUCED DIFFERENTIATION OF M1 MYELOID-LEUKEMIA CELLS

Treatment of M1 myeloid leukemia cells with leukemia inhibitory factor (LIF) causes activation of transcription factors Stat1, Stat3 and Sta t5a (signal transducers and activators of transcription). DNA-binding of Stat proteins was detectable for extended periods of time in LIF-tr eated M1 cells, which simultaneously underwent terminal differentiatio n. The relative composition of Stat factors in the protein-DNA complex es changed during time. Whereas Stat3 was activated up to 36 h during treatment with LIF, Stat5a was activated only short-termed. Similarly, high expression of the immediate early gene CIS (cytokine-inducible S H2-containing protein), a known target gene of Stat5 in hematopoietic cells, occurred only during the onset of differentiation. This suggest s a role of Stat5a in the early phase of LIF-induced differentiation a nd growth arrest of M1 cells. (C) 1998 Elsevier Science B.V.