Induction of monocytic differentiation and tumorigenicity by v-Ha-ras in differentiation arrested hematopoietic cells.
Activated ras genes are often associated with human myeloid leukemias with a monocytic differentiated phenotype. To investigate the role of the activated ras gene in leukemogenesis, a myeloid nontumorigenic cell line (FDC-P1) was infected with a selectable retroviral vector carrying the v-Ha-ras gene (H1neo). Infected FDC-P1 cells were not only tumorigenic, but also showed increased monocytic differentiation in vitro. Monocytic differentiation and tumorigenicity in vivo were correlated with several-fold increased levels of activated ras gene expression. Tumorigenic cells were arrested with respect to monocytic marker expression at a much later stage of macrophage differentiation than the parental noninfected FDC-P1 cells. These data thus suggest a model of how activated ras genes could be involved in the preferential induction of hematopoietic malignancies with a myelomonocytic phenotype.
Hibi
S
S
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Germany.
Löhler
J
J
Friel
J
J
Stocking
C
C
Ostertag
W
W
D000818:Animals; D014408:Biomarkers, Tumor; D002454:Cell Differentiation; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology*; D002999:Clone Cells; D005786:Gene Expression Regulation; D011905:Genes, ras; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006644:Histiocytes / Q000473:pathology; D016130:Immunophenotyping; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D009000:Monocytes / Q000473:pathology*; D012190:Retroviridae / Q000235:genetics; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D016173:Macrophage Colony-Stimulating Factor