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Master regulatory gene found that guides fate of blood-producing stem cells

(Philadelphia, PA) - Researchers from the University of Pennsylvania School of Medicine found that a protein called NF-Ya activates several genes known to regulate the development of hematopoietic stem cells (HSC), or blood-producing stem cells, in bone marrow. Knowing the details of this pathway may one day lead to new treatments for such blood diseases as leukemia, as well as a better understanding of how HSCs work in the context of bone-marrow and peripheral-stem-cell transplantation. The authors published their findings in the early August issue of the Proceedings of the National Academy of Sciences.

"Understanding the biology behind how the body precisely controls stem-cell fate is one of the most important issues in stem-cell biology," says senior author Stephen G. Emerson, MD, PhD, Associate Director of Clinical Research for Penn's Abramson Cancer Center and Chief of the Division of Hematology-Oncology. When HSCs divide, they have one of three fates: develop into two more stem cells, which is called self-renewal; differentiate to become one of several mature blood-cell types; or strike a balance in which one daughter cell becomes an HSC and the other becomes a mature blood-cell type.

"We know that in diseases like leukemia, the first scenario-no differentiated cells, two HCSs developing-must occur because more and more stem cells are made," explains Emerson. In conditions like bone-marrow failure, the second scenario-two differentiated cells and no HCSs-happens because the body runs out of HSCs.

"We want to figure out how this process is normally regulated in the body, so that we can learn to control it for therapeutic purposes," says Emerson. "For some clinical purposes, we might want to shift the balance so that we can grow more stem cells, for those who need them. Conversely, for patients in whom this process has gone awry, such as acute leukemia, we might block the regulatory gene to shift the balance of self-renewal versus
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
1-Aug-2005


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