The objective of this work is the characterization of the early stages of transformation induced in murine hematopoietic cells by different oncogenes. The culture system to be used are spleen-derived precursors of mast cells and of granulocyte-macrophages, both of which require WEHI-3 cell conditioned medium (WEHI-CM) for their growth. The following questions will be asked: 1. What effect do different oncogenes have on the proliferation and differentiation of mast cell and granulocyte-macrophage precursors? 2. Do oncogenes which complement each other in the transformation of fibroblasts also complement each other in the transformation of hematopoietic cells? 3. Which oncogenes or combination of oncogenes transform precursors of mast cells or granulocyte-macrophages into autocrine cells? The following properties of infected precursor cell populations will be studied: 1) their capacity to proliferate; 2) their potential to differentiate; 3) their dependence on WEHI-CM and IL-3; 4) their ability to produce growth factors; 5) their expression of proto-oncogenes and cellular genes, such as the Il-3 gene; 6) their karyotypes; 7) their in vivo tumorigenicity. A better understanding of the early (preleukemic) stages in the transformation of hematopoeitic cells may lead to methods suppressing the growth of transformed cells before they develop into autonomously growing, fully tumorigenic cells.
