1011. Growth Factor Receptors as Regulators of Hematopoiesis

Nearly 15 years have elapsed since the U.S. Food and Drug Administration last approved a major new hematopoietic cytokine. Promiscuous binding to multiple receptors, or to receptors expressed by multiple tissues, reduces growth factor specificity and promotes side effects. Here we show that hematopoiesis can be differentially regulated using receptors rather than ligands. Conditional derivatives of both fibroblast growth factor receptor-1 (F36VFGFR1) and the thrombopoietin receptor (F36VMpl) induced a sustained expansion of mouse marrow cells ex vivo, and erythroid cells in vivo. Only F36VFGFR1 supported the ex vivo expansion of short-term repopulating hematopoietic stem cells (HSCs), the ex vivo survival of long-term repopulating HSCs, and the prolonged in vivo expansion of granulocytes, monocytes and platelets. Only F36VMpl induced a response sufficiently rapid to accelerate hematological recovery from radiation-induced myelosuppression. These results establish receptors as a new class of hematopoietic regulators possessing activities unobtainable with growth factors.