The stimulatory effect of TNF on GM-CSF gene expression in JMML cells probably takes place at the transcription level, because the ribozyme treatment decreased GM-CSF mRNA.
Our findings identify the molecular basis for the autocrine TNFalpha activation of the GM-CSF gene in JMML and suggest potential novel and specific approaches for the treatment of this aggressive childhood leukemia.
Despite the presence of a measurable amount of GM-CSF in JCML cell culture supernatants, GM-CSF-specific mRNA in CFU-C cells of four cases was not detected by RT-PCR.
JCML is characterized by a spontaneous growth of granulocyte-macrophage progenitors that show a striking hypersensitivity to granulocyte-macrophage colony-stimulating factor.