Expression of the Evi-1 zinc finger gene in 32Dcl3 myeloid cells blocks granulocytic differentiation in response to granulocyte colony-stimulating factor

K Morishita, E Parganas, T Matsugi… - Molecular and Cellular …, 1992 - Am Soc Microbiol
K Morishita, E Parganas, T Matsugi, JN Ihle
Molecular and Cellular Biology, 1992Am Soc Microbiol
Expression of the Evi-1 gene is frequently activated in murine myeloid leukemias by
retroviral insertions immediately 5'or 90 kb 5'of the gene. The Evi-1 gene product is a
nuclear, DNA-binding zinc fėnger protein of 145 kDa. On the basis of the properties of the
myeloid cell lines in which the Evi-1 gene is activated, it has been hypothesized that its
expression blocks normal differentiation. To explore this proposed role, we have constructed
a retrovirus vector containing the gene and examined its effects on an interleukin-3 …
Abstract
Expression of the Evi-1 gene is frequently activated in murine myeloid leukemias by retroviral insertions immediately 5'or 90 kb 5'of the gene. The Evi-1 gene product is a nuclear, DNA-binding zinc fėnger protein of 145 kDa. On the basis of the properties of the myeloid cell lines in which the Evi-1 gene is activated, it has been hypothesized that its expression blocks normal differentiation. To explore this proposed role, we have constructed a retrovirus vector containing the gene and examined its effects on an interleukin-3-dependent myeloid cell line that differentiates in response to granulocyte colony-stimulating factor (G-CSF). Expression of the Evi-1 gene in these cells did not alter the normal growth factor requirements of the cells. However, expression of the Evi-1 gene blocked the ability of the cells to express myeloperoxidase and to terminally differentiate to granulocytes in response to G-CSF. This effect was not due to altered expression of the G-CSF receptor or to changes in the initial responses of the cells to G-CSF. These results support the hypothesis that the inappropriate expression of the Evi-1 gene in myeloid cells interferes with the ability of the cells to terminally differentiate.
American Society for Microbiology