Cellular control of in vitro progression of murine myeloid leukemia: progression accompanies acquisition of independence from growth factor and stromal cells.
The ability of bone marrow stroma cells of normal WCB6F1 (+/+) mice versus their congenic Sl/Sld stromal-defective littermates to support sustained proliferation and leukemic transformation of the growth factor-dependent myeloid cell line FDC-P1 was studied. Extensive proliferation of factor-dependent cells occurred on (+/+) normal long-term marrow culture stroma without the addition of growth factor, whereas factor-dependent cells dissipated from Sl/Sld stromal cultures after addition. The sustained proliferation that occurred on +/+ stromal layers later resulted in the appearance of factor-independent cell lines that were no longer dependent upon stroma. Factor-independent cell lines were cloned by limiting dilution and analyzed for expression of cell surface antigens to prove their origin from FDC-P1. Factor-independent cells, but not factor-dependent cells, formed tumors in syngeneic mice. These studies demonstrate a critical role for marrow stroma in the stepwise development of murine leukemia and are concordant with the previous data obtained in in vivo studies by McCool et al. that the splenic stroma of irradiated Sl/Sld mice do not support growth of Friend virus-induced preleukemic cell colonies. The present data demonstrate in a preleukemia model not induced by Friend virus complex that normal (+/+) stromal cells promote the in vitro proliferation of factor-dependent preleukemic cells and their subsequent transition to factor-independent leukemia cells, but Sl/Sld defective stroma do not efficiently promote this transition.