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 transcription factors. First identified because of its involvement in a rare chromosome translocation in human T cell acute lymphoblastic leukemia, it is now recognized to be involved in up to 25% of T cell leukemias. Normally within the hemopoietic system the gene is expressed in progenitor cells, erythroid cells, mast cells and megakaryocytes. During macrophage differentiation the level of SCL mRNA and protein becomes undetectable. To examine this further, SCL was over expressed in murine M1 cells. This resulted in perturbation of macrophage differentiation induced by leukemia inhibitory factor (LIF) and oncostatin-M (OSM) but not interleukin (IL)-6. Moreover the perturbation of LIF-induced differentiation 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 contrast the LIF receptor/gp130 heterodimer does utilize an SCL-inhibitable pathway for some elements of macrophage differentiation (e.g., lysozyme induction) but not others (e.g., M-CSF receptor induction).