Analysis of normal hematopoiesis and leukemogenesis using hematopoietic growth factor genes.

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Several growth factors are known to stimulate the differentiation and proliferation of hematopoietic cells. Among them, recently, cDNAs of human granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were cloned and the primary structures were determined. To clarify the possible roles of these factors in normal and transformed hematopoiesis, we undertook the following experiments. Firstly, several clinical samples of either hematological malignancies or solid tumors were tested about their expression of GM-CSF and G-CSF by northern hybridization. One glioblastoma, two lung cancers and one adult T cell leukemia (ATL) cases were shown to express GM-CSF mRNA. Cell lines were developed from one glioblastoma and one lung cancer and were found to secrete GM-CSF activity in their culture supernatants. Thus, these GM-CSF transcripts were suggested to be translated into GM-CSF proteins. This is the first report about the expression of GM-CSF in solid tumors. G-CSF was found to be expressed in three lung cancers and one hepatocellular carcinoma cases.In one case of lung cancer, the size of the mRMA was different from that seen normally. Secondly, to investigate the action of G-CSF to cells in vivo, we injected recombinant human G-CSF (rhG-CSF) to Bald/c mice subcutaneously for two weeks. Hypertrophic liver and spleen were observed in injected mice. RNAs were extracted from these organs and examined at low stringency by Northern hybridization with several tyrosine kinase oncogene probes. We found a transcript homologous with but distinct from fps gene, was increasedly expressed in hypertrophic liver compared to control liver.