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Crucial factors in lymphoma development and survival discovered
Date:6/23/2008

te the role of the B-cell receptor in B-cell lymphomas. They found that the presence of a functional B-cell receptor increased the development of tumors in mice with a translocated MYC oncogene.

In a series of experiments, Dr. Refaeli demonstrated that the B-cell receptor cooperated with MYC in the development of tumors both in the presence of an antigen and when no antigen was present. When no antigen was present, the mice developed a lymphoma similar to human B-cell lymphocytic leukemia.

When there was an antigen to bind to the B-cell receptor, the mice developed a lymphoma that closely resembled Burkitt's lymphoma, even to the surprising development of primary tumors in one side of the jaw. The researchers actually used an autoantigen, a molecule produced by the mouse itself, in a situation resembling autoimmune disease. Autoimmune disease increases by 50 to 200 times the chance that a person will develop B-cell lymphoma.

In experiments that both confirmed the crucial role of the B-cell receptor and pointed to potential therapies, Dr. Refaeli and his colleagues also were able to prevent and eliminate tumors by treating the mice with immunosuppressants, which block signals from the B-cell receptor. Several trials of various immunosuppressants and another inhibitor of B-cell receptor signaling have recently begun.

"Research into B-cell lymphomas has been hampered by the lack of a good mouse model," said Dr. Refaeli. "The mouse we created gives us a very good, predictive model of B-cell lymphomas, which can be used to explore not only these and related cancers, but also autoimmune disease and basic immunology."


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Contact: Adam Dormuth
dormutha@njc.org
303-398-1082
National Jewish Medical and Research Center
Source:Eurekalert

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