Myeloid leukemias result from the dysregulation of proliferation and differentiation. Hematopoietic growth factors and their receptors play a critical role in lineage commitment and differentiation of myeloid progenitor cells. Egr-1, or early growth response gene-1 is an immediate early response gene which is required for terminal differentiation of myeloid cells. In response to differentiation agents, the induction of egr-1 is rapid in response to granulocyte-colony stimulating factor (G-CSF) or 12-0 Tetradecanoylphorbol-13-acetate (TPA) and myeloid leukemic cell lines. The overall goal of this FIRST Award proposal is to use a molecular and biochemical approach to define the transcriptional regulation of egr-1 by a specific DNA-binding proteins activated by myeloid-specific differentiating agents. The myeloid cell lines will be used as a tool to study the transcriptional regulation of egr-1 by growth factors and agents which induce differentiation. The myeloid leukemic cell lines, 32Dc13, differentiatesinto granulocyte but does not proliferate in the presence of G-CSF. TF-1, a human myeloid leukemic cell line, differentiates to macrophages in response to TPA.
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