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Discovery Could Lead to New Treatments for Fighting the Disease
LOS ANGELES -- June 19, 1997 -- Reporting in the June 20 issue of the Journal Science, researchers with the U.S. Department of Veterans Affairs (VA) and UCLA have identified a surprising culprit -- an AIDS-associated virus -- which could play a critical role in triggering multiple myeloma, a malignant tumor found in bone marrow. VA researchers believe the virus, Kaposi's sarcoma-associated herpesvirus (KSHV), causes the bone marrow cancer by infecting non-malignant cells. The discovery has implications for therapy, prevention and a possible cure for the disease.
"This is the first time a virus has been linked to this cancer," said senior author and chief of oncology James R. Berenson, M.D., of the West Los Angeles VA Medical Center. "We now have a new target for developing treatments and possibly a vaccine to prevent myeloma." Berenson's VA laboratory served as the site for this groundbreaking research.
Using advanced PCR (a technology used to produce copies of genetic material), Drs. Berenson, Matthew B. Rettig (also of VA and first author of the Science paper) and colleagues detected KSHV in certain bone marrow cells of 15 multiple myeloma patients. However, it was found not to be present in similar cells from 10 healthy volunteers or 16 patients with other types of cancer involving bone marrow. KSHV was first identified in AIDS patients with the skin cancer Kaposi's sarcoma (KS).
Surprisingly, the team did not find KSHV in the malignant plasma cells, but they were in the "dendritic" cells -- virally infected non-malignant cells -- which serve as a kind of nurturing soil to plasma cells, releasing proteins that promote their growth. "The virus infects the soil instead of the seed," said Dr. Rettig "and this virus-infected soil may drive the uncontrolled plasma cell growth," he added.
Multiple myeloma is a cancer of plasma cells which produce antibodies to fight infection. Malignant plasma cells produce large amounts of an abnormal antibody detectable in the blood of myeloma patients, while levels of normal antibodies drop sharply. Plasma cells are a critical part of the body's immune system. They are manufactured in the bone marrow and then move into the bloodstream. The bone marrow is the body's factory for producing blood cells.
Among blood cancers, only lymphoma is more common than multiple myeloma.
Some 50,000 Americans have myeloma at any given time, with 15,000 new cases diagnosed annually. It's estimated the bone marrow based cancer will cause about 10,000 deaths this year. Although often described as a disease of the elderly, 35-50 percent of those diagnosed will be under the age of 60. And, the risk of developing myeloma is twice as great among African-Americans than in whites.
The disease is characterized by bone pain and fractures, kidney failure, anemia, and infections. Despite advances in chemotherapy, Berenson emphasized, there is no cure. The average survival time after diagnosis has remained unchanged at about three years.
He also noted that about a million Americans have "monoclonal gammopathy of undetermined significance" (MGUS), a precursor to multiple myeloma. In MGUS, multiple myeloma's abnormal antibody is present in the blood of people who are asymptomatic or show no signs of the disease. About 25 percent of people with this condition ultimately develop the cancer. In two of the eight study subjects who had MGUS, Berenson's team found KSHV in the dendritic cells. "We believe the presence of this virus may be what triggers development of myeloma from MGUS," he said.
Until the 1980s, Kaposi's sarcoma was a rare skin cancer, found primarily in older men or people with organ transplants. Then, doctors began to notice more cases of KS in AIDS patients. KSHV was discovered in 1994 and infects many people who have the human immunodeficiency (HIV) virus, although not all those patients develop KS. Some evidence suggests that multiple myeloma may become more common in people with HIV, than with the general population.
"Our findings provide a link," Berenson said, "suggesting that these patients might be increasingly susceptible to myeloma as new therapies for HIV allow them to live longer." In addition, about three percent of all people over 70 and 10 percent of those over 80 have MGUS, he added, so myeloma can be expected to increase as Americans age.
Dr. Berenson is a professor of medicine and a co-director of the Jonsson Comprehensive Cancer Center at UCLA. Last year, he led a study (published in the New England Journal of Medicine) that showed pamidronate markedly reduced bone destruction, resulting in substantial clinical benefits in treating multiple myeloma. On the basis of that single study, the Food and Drug Administration granted approval to the use of pamidronate as a treatment for the disease.
Berenson and colleagues are now working to develop both non-toxic drugs to fight KSHV and a vaccine aimed at preventing infection by the virus. "Identifying the cause for any type of disease is the key to its eventual control. Our findings are an important step towards that effort."
VA research provides improved medical care for veterans, as well as the population in general. Through its unique affiliation with medical school s, VA plays a crucial role in educating future physicians in research and clinically oriented areas.
More information on the virus
theory can be found at: The Myeloma Foundation of South Africa web site. http://www.geocities.com/hotsprings/5137/index.html
This site discusses the stealth virus and how it manifests itself and possibly may cause myeloma. http://www.ccid.org/