Modulation of the activation status of Stat5a during LIF-induced differentiation of M1 myeloid leukemia cells

Abstract

Treatment of M1 myeloid leukemia cells with leukemia inhibitory factor (LIF) causes activation of transcription factors Stat1, Stat3 and Stat5a (signal transducers and activators of transcription). DNA-binding of Stat proteins was detectable for extended periods of time in LIF-treated M1 cells, which simultaneously underwent terminal differentiation. The relative composition of Stat factors in the protein-DNA complexes 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 SH2-containing protein), a known target gene of Stat5 in hematopoietic cells, occurred only during the onset of differentiation. This suggests a role of Stat5a in the early phase of LIF-induced differentiation and growth arrest of M1 cells.