Submitted January 26, 2006
Accepted July 18, 2006
Growth factor receptors as regulators of hematopoiesis
Michael Weinreich, Ingrid Lintmaer, Linlin Wang, H. Denny Liggitt, Michael A. Harkey, and Carl Anthony Blau*
Division of Hematology, Department of Medicine, University of Washington Seattle, WA
Department of Comparative Medicine, University of Washington Seattle, WA
Division of Transplantation Biology, Fred Hutchinson Cancer Research Center, Seattle, WA
* Corresponding author; email: tblau{at}u.washington.edu.
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.
