Target-cell specificity of hematopoietic regulatory proteins for different clones of myeloid leukemic cells: two regulators secreted by Krebs carcinoma cells.

The normal myeloid hematopoietic regulatory proteins include one class of proteins that induces viability and multiplication of normal myeloid precursor cells to form colonies (called MGI-1 = CSF or IL-3) and another class (called MGI-2 = DF) that induces differentiation of normal myeloid precursors without inducing cell multiplication. Different clones of myeloid leukemia cells can differ in their response to these regulatory proteins. The present experiments characterize proteins secreted by Krebs ascites carcinoma cells that induce differentiation of 2 different types of myeloid leukemic cell clones (clones II and 7-M12). The results indicate the following: (1) Krebs cells produce 2 distinct and separable proteins, each inducing differentiation in one of the leukemic clones. (2) One protein induced differentiation of clone-II myeloid leukemic cells and of normal myeloid precursor cells was free of any colony-inducing (MGI-1 = CSF or IL-3) activity, bound to double-stranded mammalian DNA, and was thus a differentiation-inducing protein MGI-2. This MGI-2 protein (MGI-2A) was purified to a single silver-stained band on an SDS polyacrylamide gel. (3) The other protein induced differentiation of clone 7-M12 myeloid leukemic cells, did not bind to double-stranded DNA and could not be separated from the myeloid growth-inducing protein MGI-1GM (GM-CSF) after 6 steps of purification including high-pressure liquid chromatography. The use of specific antisera confirmed that the protein which induced differentiation of clone 7-M12 leukemic cells was MGI-1 GM. The results show that Krebs ascites tumor cells produce 2 different myeloid hematopoietic regulatory proteins that differ in their target specificity for different clones of myeloid leukemic cells.