THROMBOPOIETIN EXPANDS ERYTHROID, GRANULOCYTE-MACROPHAGE, AND MEGAKARYOCYTIC PROGENITOR CELLS IN NORMAL AND MYELOSUPPRESSED MICE

Thrombopoietin (Tpo), the ligand for the proto-oncogene receptor c-Mpl , increases megakaryocyte size, ploidy, and surface expression of plat elet-specific glycoproteins, is inversely related to platelet mass, an d is a potent in vivo stimulus of platelet production. However, severa l features of c-mpl biology, and that of its viral counterpart v-mpl, suggest that the action of Tpo may not be strictly limited to megakary ocytopoiesis. To investigate the possibility that Tpo might affect a m ultitude of cell lineages, we studied the effects of in vivo administr ation of the hormone on multiple types of marrow and splenic clonogeni c hematopoietic progenitors. We report that Tpo acts to expand BFU-E, CFU-GM, and CFU-Mk and redistribute CFU-E in normal mice and to hasten the recovery of all of these progenitor cell types in myelosuppressed animals. These findings argue that the hematopoietic progenitor cell compartment responds to Tpo as a whole and that the in vivo effects of Tpo administration may be more wide-ranging than previously anticipat ed.