TNF-ALPHA ACTS IN SYNERGY WITH GM-CSF TO INDUCE PROLIFERATION OF ACUTE MYELOID-LEUKEMIA CELLS BY UP-REGULATING THE GM-CSF RECEPTOR AND GM-CSF GENE-EXPRESSION

Acute myeloid leukemia (AML) cells are dependent for their survival an d proliferation on hematopoietic growth factors. As tumor necrosis fac tor alpha (TNFalpha) can increase the proliferation of primary culture s of AML cells, we have investigated the effect of TNFalpha on the aut ocrine and/or paracrine growth control by one of the major AML growth factor, granulocyte-macrophage colony-stimulating factor (GM-CSF). Fir st, a panel of AML cells were analysed with respect to their prolifera tive response to TNFalpha. We provide experimental evidence that TNFal pha induces both GM-CSF gene expression and up-regulation of high-affi nity GM-CSF membrane receptor in TNFalpha-responsive cells. This effec t is not restricted to the malignant phenotype, although it could acco unt for the selective growth advantage of the leukemic clone over the normal cells upon TNFalpha stimulation.