ABSTRACT
Original concepts of tumor cell autonomy were influenced by clinical and pathologic criteria recognizing the monotony of a cell population whose normal boundaries had been exceeded in the organism with cancer. The participation of leukemia cells in microenvironmental cell-mediated augmentation of their own growth was recently reported by Griffin and colleagues. These investigators observed that purified AML cells constitutively secreted into culture medium significant quantities of interleukin-1, which could stimulate the production of leukemic cell stimulatory GM-CSF and G-CSF from endothelial cells. Therefore, local excess of microenvironmental growth factors for leukemic cells is mandated by their production of mediator(s) that regulate stromal cell growth factor production. In order to pursue the possibility that blunted signal transduction through the cyclic AMP pathway might be one mechanism for clonal dominance by myeloid leukemia cells, it was necessary to further define the components of cyclic AMP signal transduction.
