THE SCL TRANSCRIPTION FACTOR AND DIFFERENTIAL REGULATION OF MACROPHAGE DIFFERENTIATION BY LIF, OSM AND IL-6

The SCL gene is a member of the helix-loop-helix family of transcripti on factors. First identified because of its involvement in a rare chro mosome translocation in human T cell acute lymphoblastic leukemia, it is now recognized to be involved in up to 25% of T cell leukemias. Nor mally within the hemopoietic system the gene is expressed in progenito r cells, erythroid cells, mast cells and megakaryocytes. During macrop hage differentiation the level of SCL mRNA and protein becomes undetec table. To examine this further, SCL was over expressed in murine M1 ce lls. This resulted in perturbation of macrophage differentiation induc ed by leukemia inhibitory factor (LIF) and oncostatin-M (OSM) but not interIeukin (IL)-6. Moreover the perturbation of LIF-induced d differe ntiation applied to some components of macrophage differentiation but not others. This suggests that signaling through the gp130 homodimer ( as occurs with IL-6) does not utilize an SCL-inhibitable pathway. In c ontrast the LIF receptor/gp130 heterodimer does utilize an SCL-inhibit able pathway for some elements of macrophage differentiation (e.g., ly sozyme induction) but not others (e.g., M-CSF receptor induction).