INHIBITION OF FRIEND-CELLS PROLIFERATION BY SPI-1 ANTISENSE OLIGODEOXYNUCLEOTIDES

The spi-1 proto-oncogene encodes the transcription factor PU.1 which i s normally expressed in all hematopoietic cell lineages except in T ce ll lines. During the murine acute erythroleukemia induced by the Frien d retrovirus, SFFV, spi-1 deregulation by insertional mutagenesis resu lts in the overexpression of Spi-1/PU.1 in the malignant proerythrobla stic cell. To assess the Spi-1 role in the proliferation and the diffe rentiation arrest of the Friend tumor cells we inhibited spi-1 gene ex pression in two Friend cell lines by using antisense oligodeoxyribonuc leotides. Proliferation and cloning efficiency of both cell lines were significantly inhibited by spi1 antisense. This antiproliferative eff ect was not related to an apparent maturation of erythroleukemic cells demonstrating that repression of spi-1 expression is not sufficient p er se to restore the ability of the proerythroblastic cells to spontan eously differentiate in mature erythroblasts. These data suggest that the spi-1 gene would be involved in the Friend leukemic process by pro moting the proerythroblast to proliferate.