Long-term and dependent growth of human leukemic blast cells with granulocyte-macrophage differentiation in vitro.

A clonal growth of leukemic cells from the bone marrow of a patient with acute myeloid leukemia was observed in vitro for more than 20 months. Cytochemical and electron microscopic studies of the cells growing in vitro demonstrated that they were blast cells, differentiated granulocytes, and macrophages. They showed complete dependence on granulocyte-macrophage colony-stimulating factor for colony formation in agar. In addition to the presence of granulocytic colonies, some showed granulocyte-macrophage characteristics, suggesting that bipotential cells were also involved in long-term growth. Initially, they showed localized proliferation on or around giant fibroblast-like cells. Even after constant growth was established, attempts to transfer these cells were unsuccessful, and their growth was confined to the original flasks. These observations seen to indicate that their growth was not autonomous but dependent on the adherent cells in the flasks. This was also supported by a coculture experiment in which the cells were demonstrated to proliferate for 4 months only in the presence of normal bone marrow particles and bone marrow particle-derived feeder layers. These results suggest that, in some cases, long-term growth of leukemic cells can be induced in vitro by the cocultivation of bone marrow stromal cells.