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Knocking out SHIP gene improves success of allogeneic bone marrow transplants in mice

Tampa, FL (March 15, 2002) Mice lacking a gene known as SHIP did not reject fully mismatched bone marrow transplants from other mice and most survived without complications following the transplants, a study by researchers at the University of South Florida and H. Lee Moffitt Cancer Center & Research Institute found. The study is published in the March 15 issue of the journal Science.

The research suggests ways to increase the effectiveness and use of bone marrow transplants from related and unrelated donors known as allogeneic transplants in treating cancers, genetic deficiencies and autoimmune diseases.

In mice, the SHIP gene plays a key role in helping the body distinguish between itself and tissue from a donor other than self. When the gene is missing or knocked out, the mouse's immune system apparently fails to recognize the donor's bone marrow as a foreign substance and allows the graft to survive.

"If the SHIP gene plays a similar role in humans, then drugs to temporarily block SHIP could be given to a patient before they undergo an allogeneic bone marrow transplant so they won't reject the transplant and the transplant won't attack them," said William Kerr, PhD, lead investigator for the study. Dr. Kerr is an associate professor of oncology and biochemistry at USF and a member of Moffitt Cancer Center's Immunology Program.

In the USF/Moffitt study, less than a third of the mice with the SHIP gene survived the allogeneic bone marrow transplants. But, Dr. Kerr's team found that 85 percent of the SHIP-deficient mice survived without two major complications that limit the success of allogeneic bone marrow transplants. First, the mice did not reject the transplant. Secondly, in the weeks following the transplants, the grafts did not launch an immune attack against the mice's bodies a potentially life-threatening reaction known as graft-versus-host disease.

"This is an exciting breakthrough because a molecular target, s
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Contact: Anne DeLotto Baier
abaier@hsc.usf.edu
813-974-3300
University of South Florida Health
14-Mar-2002


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