THROMBOPOIETIN EXPANDS ERYTHROID PROGENITORS, INCREASES RED-CELL PRODUCTION, AND ENHANCES ERYTHROID RECOVERY AFTER MYELOSUPPRESSIVE THERAPY

Thrombopoietin (TPO), the ligand for the receptor protooncogene c-mpl, has been cloned and shown to be the critical regulator of platelet pr oduction, Several features of c-Mpl expression, including its presence on erythroid cell lines, and the panmyeloid transformation characteri stic of myeloproliferative leukemia (MPL) viral disease led us to inve stigate whether this receptor-ligand system may play a role in erythro poiesis. We report that although TPO alone did not support the growth of either early or late erythroid progenitors, it acted in synergy wit h erythropoietin to expand these populations, Moreover, while the effe cts on erythropoiesis in normal animals were modest, TPO greatly expan ded the number of erythroid progenitors and blood reticulocytes and wa s associated with accelerated red cell recovery in myelosuppressed mic e, Together, these data strongly suggest that erythroid progenitors re spond to TPO and that this newly cloned cytokine, critical for platele t production, can augment erythropoiesis in states of marrow failure.