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Expression and downregulation of cytotoxic cell protease 1 or Granzyme 'B' transcripts during myeloid differentiation of interleukin-3- dependent murine stem cell lines

IN Hampson, MA Cross, CM Heyworth, L Fairbairn, E Spooncer, GJ Cowling and TM Dexter

Cancer Research Campaign Department of Experimental Hematology, Paterson Institute for Cancer Research, Withington, Manchester, UK.

Using the technique of differential cDNA library screening, we have molecularly cloned a gene that is highly expressed in an undifferentiated myeloid multipotent and growth factor-dependent stem cell line (FDCP-Mix) and that downregulates as these cells are induced to differentiate along monocytic, granulocytic, and erythroid cell lineages. Sequence analysis of this gene has shown homology with a previously cloned gene, cytotoxic cell protease 1 (CCP1 or Granzyme 'B'), that has been shown to be expressed only in thymocytes, activated T cells, a mast cell line, and peritoneal exudate leukocytes. In situ hybridization, Northern blot analysis, and nuclear run-off assay has confirmed that expression of CCP1 is restricted to the phenotypically primitive multipotent undifferentiated. FDCP-Mix cells that are undergoing self-renewal in the presence of growth factors such as interleukin-3.

Volume 80, Issue 12, pp. 3097-3105, 12/15/1992
Copyright © 1992 by The American Society of Hematology


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