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University of Pittsburgh discovers genetic 'shut down' trigger in healthy immune cells

PITTSBURGH, May 9 -- A fundamental genetic mechanism that shuts down an important gene in healthy immune system cells has been discovered that could one day lead to new therapies against infections, leukemia and other cancers. Results of a University of Pittsburgh School of Medicine study on the mechanism, called a somatic stop-codon mutation, are being reported today in the online journal PLoS ONE, published by the Public Library of Science.

"This kind of loss-of-function mutation can be very dangerous, and it is the first such mutation that has been identified in normal immune cells in blood," said Bora E. Baysal, M.D., Ph.D., assistant professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine. "We did control experiments for two years to make sure it was real and not a technical error."

Dr. Baysal and his colleagues tested 180 samples, including blood from healthy individuals and other material from those with childhood leukemia, looking at specific portions of DNA in immune cells known as monocytes, natural killer cells and lymphocytes. These cells are key to the bodys immune response against infection and disease. The investigators found somatic stop-codon mutations in an average of 5.8 percent of crucial portions of genetic material that deliver instructions from DNA, called messenger RNA, in normal blood samples and in a quarter of leukemia samples.

"DNA is the blueprint for all living cells. It carries the genetic code for most biological functions and is passed virtually unchanged from generation to generation," said Dr. Baysal, who also is an associate investigator at the university-affiliated Magee-Womens Research Institute. "Harmful alterations in the code mutations can produce genetic disorders and play an important role in the development of cancer. Normal cells such as monocytes, lymphocytes and natural killer cells have many mechanisms to recognize and repair m
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Contact: Michele Baum
baummd@upmc.edu
412-647-3555
University of Pittsburgh Schools of the Health Sciences
9-May-2007


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