Spi-1/PU.1 proto-oncogene induces opposite effects on monocytic and erythroid differentiation of K562 cells.

Spi-1/PU.1 is a hematopoietic transcription factor of the Ets family. To analyze the effects of ectopic expression of spi-1 on the proliferation/differentiation of human myeloid leukemia cells, K562 cells were stably transfected with a spi-1 expression vector. The transfected cell lines expressed elevated levels of spi-1 mRNA and protein and high Spi-1-DNA binding activity. The spi-1 transfected cells showed reduced growth rates and reduced clonogenic cell growth. When the erythroid and monocytic differentiation markers were analyzed, spi-1 overexpression resulted in opposite effects: erythroid differentiation was significantly inhibited in spi-1 transfectants, while spi-1 overexpression increased the monocytic differentiation of cells. These results indicate a differential role of Spi-1 on the differentiation of human myeloid leukemia cells.