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Y Shimada, G Migliaccio, S Ruscetti, JW Adamson and AR Migliaccio
Laboratory of Hematopoietic Growth Factors, Lindsley F. Kimball Research
Institute, New York Blood Center, New York 10021.
Friend spleen focus-forming virus (F-SFFV) is a replication-defective
retrovirus that induces a multistage erythroleukemia in mice. In the first
stage, expression of the SFFV envelope glycoprotein results in erythroid
hyperplasia. Subsequently, the F-SFFV integrates near the Spi- 1 gene and
activates its expression, resulting in immortalized cells that represent a
second stage in the disease process. We report here that media conditioned
by erythroleukemia cell lines or leukemic spleen cells induced by the
polycythemia-inducing strain of F-SFFV (F-SFFVp), but not medium
conditioned by SFFVp-induced hyperplastic spleens, promote the
proliferation of normal granulocyte-macrophage progenitor cells and of
granulocyte-macrophage colony-stimulating factor (GM-CSF)- and/or
interleukin-3 (IL-3)-dependent cell lines. The colony- stimulating activity
of the conditioned media from four of five of the lines studied was
neutralized by antibodies specific for IL-3 and/or GM- CSF, and IL-3 and
GM-CSF-specific mRNA could be detected in the cells after amplification by
the polymerase chain reaction. No rearrangements of the IL-3 or GM-CSF
genes were observed by Southern blot analysis. However, as previously shown
for SFFV-induced cell lines, the Spi-1 gene was expressed in all of these
cells. Because the Spi-1 gene encodes a transcription factor whose cognate
sequences are present in the promoter region of many hematopoietic growth
factor genes, including IL-3 and GM-CSF, Spi-1 activation may be inducing
the expression of these genes.
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| Copyright © 1992 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||