Autocrine production of pre-B-cell stimulating activity by a variety of transformed murine pre-B-cell lines.

Current evidence suggests that the proliferation and differentiation of normal pre-B-cells may be regulated by interactions with mesenchymally derived stromal cells. The nature of these cell-cell interactions has not yet been fully elucidated, but the involvement of pre-B-cell stimulating factors produced by various mesenchymal cell lines has recently been demonstrated in the murine system. In this model, transformed pre-B-cells differ from their normal counterparts in their acquisition of autonomous growth potential, as seen by an ability to be maintained in vitro in the absence of mesenchymal cell feeders. To test the hypothesis that autonomy might be associated with autocrine growth factor production, we tested the ability of a spontaneous pre-B-cell transformant (H9 cells) and two independently derived Abelson murine leukemia virus transformed pre-B-cell lines to produce pre-B-cell stimulating factors. All three lines released activities that stimulated the proliferation of themselves or H9 cells when cultured at low cell densities. One of the three transformed pre-B-cell lines could also substitute for mesenchymal feeders to stimulate normal pre-B-cells. Time course studies of an evolving Abelson murine leukemia virus transformant showed that the production of an autocrine pre-B-cell growth factor increased concomitantly with the acquisition of autonomous growth potential suggesting a relationship between these two phenotypic changes. Preliminary characterization of the growth factor responsiveness of H9 cells and the nature of the autostimulatory activity produced by this line suggested its nonidentity with any known hemopoietic growth factor. Activation of autocrine growth factor production appears to be a common event in the evolution of malignant pre-B-cells arising through different oncogenic mechanisms and may therefore be relevant to the pathogenesis of human acute lymphoid leukemia.