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 and proliferation on hematopoietic growth factors. As tumor necrosis factor alpha (TNF alpha) can increase the proliferation of primary cultures of AML cells, we have investigated the effect of TNF alpha on the autocrine and/or paracrine growth control by one of the major AML growth factor, granulocyte-macrophage colony-stimulating factor (GM-CSF). First, a panel of AML cells were analysed with respect to their proliferative response to TNF alpha. We provide experimental evidence that TNF alpha induces both GM-CSF gene expression and up-regulation of high-affinity GM-CSF membrane receptor in TNF alpha-responsive cells. This effect is not restricted to the malignant phenotype, although it could account for the selective growth advantage of the leukemic clone over the normal cells upon TNF alpha stimulation.