Lymphoma is the most common blood cancer and the third most common childhood cancer in the United States. Although there are many types of lymphoma, they all originate in the white blood cells (lymphocytes) that are part of the immune system. These cells are meant to protect the body against infection, but sometimes they become diseased themselves. The exact cause of this cancer is unknown, but now researchers funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have made a scientific advance that could lead to new therapies.
Rafael Casellas, Ph.D., and his team in the Genomics and Immunity Group within the Molecular Immunology and Inflammation Branch of NIAMS, along with Michael Potter, M.D., and his group in the Laboratory of Cancer Biology and Genetics of the National Cancer Institute, looked into the role of a certain kind of white blood cell, known as a B cell, in the origin of lymphoma. Their findings were recently published in the Journal of Experimental Medicine.
Existing research has shown that more than 95 percent of all lymphomas diagnosed in the western world are of B cell origin. In recent years, an enzyme in B cells called activation-induced cytidine deaminase, or AID, has been linked to the formation of tumors.
Dr. Casellas and his colleagues set out to pinpoint how AID acts on B cells to divert them from their mission of making protective antibodies and instead cause them to become malignant cancer cells. The team altered levels of AID in the B cells of a mouse and observed the way the cells reacted with both more and less of the enzyme than normal. Tumor development was drastically diminished in mice whose cells expressed half of the normal AID activity. At the same time, the beneficial immune responses of these cells with lower levels of AID were only slightly altered.
The set of experiments conducted by Drs. Casellas, Potter, and their teams demonstrates that the incidence of lymphoma tumors is directly proportional to the amount of AID in the B cell. This research suggests that AID can be targeted for future therapies to fight lymphoma and to alleviate the suffering it causes.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at 301-495-4484 or 877-22-NIAMS (toll-free call) or visit the NIAMS Web site at http://www.niams.nih.gov.
AID expression levels determine the extent of cMyc oncogenic translocations and the incidence of B cell tumor development. Takizawa M, Tolarov' H, Li Z, Dubois W, Lim S, Callen E, Franco S, Mosaico M, Feigenbaum L, Alt FW, Nussenzweig A, Potter M, Casellas R. J Exp Med. 2008 Sep 1;205(9):1949-57. Epub 2008 Aug 4. PMID: 18678733