Abstract
Thrombopoietin (TPO), the ligand for c-mpl receptor, has been purified by investigators in a number of laboratories using different strategies. TPO supports the proliferation, differentiation and maturation of megakaryocytes and their precursors, and results in their terminal fragmentation into platelets. TPO appeared initially to act as a lineage-specific late-acting hematopoietic growth factor, like the effects of erythropoietin and granulocyte colony-stimulating factor on erythropoiesis and myelopoiesis, respectively. However, several groups have now shown that myelopoiesis and erythropoiesis are also affected by TPO. TPO acted in synergy with EPO to increase the growth of erythroid porliferation from bone marrow cells. Furthermore, TPO interacted with the steel factor, the ligand for flk2/flt3, and/or interleukin-3 to support the formation of multiple types of hematopoietic colonies from a highly purified population of hematopoietic progenitors. Mice lacking c-mpl revealed a reduced number of hematopoietic progenitors including multipotential, blast cell and committed progenitors as well as a deficiency of megakaryocytic progenitors in the culture. The administration of TPO ameliorated the depth and duration of thrombocytopenia, and the severity of leukopenia and anemia in mice treated with a combination of carboplatin and irradiation. These observations indicate that the effects of TPO on hematopoiesis are greater than initially anticipated. TPO may be an important cytokine for the manipulation of human hematopoietic stem cells in synergy with other early-acting factors.
