HUMAN THROMBOPOIETIN - GENE STRUCTURE, CDNA SEQUENCE, EXPRESSION, ANDCHROMOSOMAL LOCALIZATION

Thrombopoietin (TPO), a lineage-specific cytokine affecting the prolif eration and maturation of megakaryocytes from committed progenitor cel ls, is believed to be the major physiological regulator of circulating platelet levels. Recently we have isolated a cDNA encoding a ligand f or the murine c-mpl protooncogene and shown it to be TPO. By employing a murine cDNA probe, we have isolated a gene encoding human TPO from a human genomic library. The TPO locus spans over 6 kb and has a struc ture similar to that of the erythropoietin gene (EPO). Southern blot a nalysis of human genomic DNA reveals a hybridization pattern consisten t with a single gene locus. The locus was mapped by in situ hybridizat ion of metaphase chromosome preparations to chromosome 3q26-27, a site where a number of chromosomal abnormalities associated with thrombocy themia in cases of acute myeloid leukemia have been mapped. A human TP O cDNA was isolated by PCR from kidney mRNA. The cDNA encodes a protei n with 80% identity to previously described murine TPO and is capable of initiating a proliferative signal to murine interleukin 3-dependent BaF3 cells expressing the murine or human TPO receptor.