The Purification and Cloning of Human Thrombopoietin

Abstract

For more than 20 years, numerous groups have attempted purification of thrombopoietin (TPO) from the plasma of thrombocytopenic or pancytopenic animals and humans (reviewed in refs. 1–3, and Chapter 5). These efforts were based on observations, dating from the late 1950s, of a factor in such plasma that specifically regulates platelet production (4,5). The observation that nephrectomized mice become thrombocytopenic led others to attempt isolation of TPO from kidney cell-culture medium (3). Because of the lack of a specific TPO assay and the extremely low level of endogenous TPO in thrombocytopenic plasma or cell-culture media, these efforts were historically of limited success. However, these experiments provided information that, when combined with the discovery of a putative TPO receptor, Mpl, aided in the relatively rapid isolation of TPO from the plasma of aplastic animals by several groups, who reported the isolation and cloning of TPO in 1994 (6–10). During the same period, two different groups succeeded in purifying TPO using conventional chromatographic procedures (see Chapter 9).