THE ROLE OF SOLUBLE GROWTH-FACTORS IN INDUCING TRANSIENT GROWTH AND CLONAL EXTINCTION OF STROMA CELL-DEPENDENT ERYTHROBLASTIC LEUKEMIA-CELLS

A coculture system of a murine erythroblastic leukemia cell line (ELM- D) with its supportive stromal cell line (MS-5) was established. Long- term growth of ELM-D cells is strictly stroma cell dependent. Interact ion between stem cell factor (SCF) and its receptor, c-kit, was demons trated to be important for stroma cell-dependent growth by anti c-kit neutralizing monoclonal antibody (mAb) inhibition experiments. Signifi cantly, soluble growth factors such as granulocyte-macrophage colony-s timulating factor (GM-CSF), interleukin-3 (IL-3) or SCF of MS-5 stroma l cells (MS-5 CM) could replace the requirement of stroma cells for a considerable period. However, ELM-D cells maintained in these growth f actors underwent clonal extinction after 3-6 weeks unless contact with stroma was re-established. Furthermore, IL-3 or GM-CSF acted in a dom inant manner in inducing cell death in the presence of stroma cells. C ells showing clonal extinction undergo programmed cell death and do no t differentiate. These altered growth properties of ELM-D cells expose d to soluble growth factors or to stroma cells appear to be analogous to those described for T or B cells primed by antigen presenting cells and then grown in growth factors.