Mouse lymphoid leukemias: symbiotic complexes of neoplastic lymphocytes and their microenvironments

Of 17 primary lymphoid leukemias of the mouse, 15 symbiotic cell lines were isolated by the explantation of leukemia tissues from which free leukemia cells had been mechanically removed. In vitro survival and growth of symbiotic leukemia cells depended on close association with the adherent cells from the initial explants or other sources. Pseudo-emperipolesis was a remarkable morphologic manifestation of symbiosis common to all cell lines, i.e., the leukemia cells were beneath the adherent cells in close contact. Cell interaction in symbiotic leukemias was studied with a representative symbiotic leukemia AKRL-3 and a cell line B6TE-A from normal thymic epithelium. Failure of the culture supernatant of the adherent cells to support the growth of leukemia cells indicated that the function of the adherent cells was mediated by close cell contact. During the culture, many symbiotic cell lines changed growth patterns and eventually grew independently. Consistent isolation of symbiotic cell lines from most primary leukemias, as well as consideration of the role of the thymus in leukemogenesis, may indicate that the lymphoid leukemias are basically symbiotic complexes of neoplastic lymphocytes and their microenvironments in their natural history. Similar lymphoepithelial cell complexes were isolated recently from normal murine thymus.