BOTH STROMA AND STEM-CELL FACTOR MAINTAIN LONG-TERM GROWTH OF ELM ERYTHROLEUKEMIA-CELLS, BUT ONLY STROMA PREVENTS ERYTHROID-DIFFERENTIATIONIN RESPONSE TO ERYTHROPOIETIN AND INTERLEUKIN-3

Defining how the stromal requirements of hematopoietic progenitors cha nge during leukemia progression is an important topic that is not well understood at present. The murine ELM erythroleukemia is an interesti ng model because the erythroid progenitors retain dependence on bone m arrow-derived stromal cells for long-term growth in vitro, and they al so undergo erythroid differentiation in the presence of erythropoietin (EPO) and interleukin-l (IL-3). In this report, we have shown using n eutralizing antibodies that stem cell factor (SCF), insulin-like growt h factor (IGF)-1, and integrin signaling pathways are all involved. We then determined whether ELM cells can be maintained long-term without stroma in various combinations of growth factors produced by stroma c ells or growth factors for which ELM cells have receptors. This showed that ELM cells could be maintained with high efficiency in SCF alone; furthermore, the cells remained absolutely SCF-dependent and did not become more tumorigenic than cells maintained on stroma. In contrast, ELM cells underwent clonal extinction when serially cloned in IGF1; an y cells that survived long-term growth in IGF-1 were found to be IGF1- independent. One important difference between maintaining ELM cells on stroma and growth in SCF is that stroma reversibly inhibits their dif ferentiation in response to EPO and IL-3, whereas SCF does not. (C) 19 98 by The American Society of Hematology.