Erythropoietin

This chapter focuses on advances made in understanding the expression, structure and biological functions of EPO and the EPO receptor (EPOR), particularly at the molecular level. Erythropoietin receptors are expressed on the placenta, suggesting that they may be involved in maternal-to-fetal transfer of EPO. The EPOR cDNA has been ectopically expressed in IL-3-dependent cell lines and this expression enables the cells to grow in the presence of either IL-3 or EPO, demonstrating that EPO and the EPOR can also stimulate cell proliferation in nonerythroid hematopoietic cell lines. Expression of the EPOR cDNA in IL-3-dependent cell lines, such as BA/F3 or 32D, rendered these cells EPO-responsive, demonstrating that the cloned receptor is functional in terms of stimulating cell proliferation. Sequence analysis of genomic DNA isolated from affected individuals demonstrated that they carry a mutation in one allele of the EPOR that introduces a premature stop codon in the cytoplasmic tail of the receptor, deleting the last 70 amino acids.