Importantly, using our well-established Spi1 transgenic leukemia mouse model, we demonstrate that Spi1 overexpression also induces senescence in erythroid progenitors of the bone marrow <i>in vivo</i> before the onset of the pre-leukemic phase of erythroleukemia.
Purine Rich Box-1 (PU.1)/ SFFV Proviral Integration Site-1 (Spi-1) is an Ets-family transcription factor, which was first characterized as an oncogene in Friend's murine erythroleukemia, and subsequently, as a transcriptional regulator of myeloid promoters.
Retroviral insertional activation of Fli-1 and Spi-1/PU.1, as well as loss of tumour suppressor genes such as p53 or p45 NFE2 have been shown to be critical for the induction and progression of Friend virus-induced erythroleukemias.
This strict specificity of integration sites suggests that Fli-1 and Spi-1 may be functionally distinct and transactivate different downstream genes during the progression of multistage Friend erythroleukemia.
Three of the ets oncogene superfamily members v-ets, Spi-1/PU.1 and Fli-1, have been shown to be directly involved in retroviral-mediated acute erythroleukemias.
In the multistage erythroleukemias induced by the various strains of Friend leukemia virus, the analysis of proviral-integration events has led to the identification of two genes, Fli-1 and Spi-1, both novel members of the ets oncogene family of transcription factors.
Three probes were used for the chromosomal assignment of the human SPI1 oncogene: cDb1 and RaB2 correspond respectively to murine Spi1 and human SPI1 cDNA probes; C45a6B probe is a murine genomic DNA sequence located in the Spi1 5' region and is known as a major SFFV integration site in murine erythroleukemia cells.