Researchers have fingered a virus as the culprit behind a bone marrow tumor called multiple myeloma. While viruses already have been linked to other cancers, the modus operandi of this one--Kaposi's sarcoma-associated herpesvirus (KSHV)--is unusual: The virus appears to work behind the scenes as a cellular puppet master, triggering tumor growth from neighboring cells. The finding, reported in tomorrow's issue of Science,* could steer researchers to new therapies for multiple myeloma, which strikes 13,000 people every year in the United States alone and usually kills its victims within 3 years.
KSHV is already under suspicion as the cause of Kaposi's sarcoma, a cancer that afflicts many AIDS patients. But unlike the malignant cells of Kaposi's and all the other cancers thought to be caused by viruses, multiple myeloma cells--derived from the bone marrow's antibody-producing plasma cells--don't seem to be directly infected. Instead, a research team led by oncologists James Berenson and Matthew Rettig of the Veterans Affairs West Los Angeles Medical Center has found evidence that KSHV is lurking in adjacent dendritic cells, a subset of macrophages found in the bone marrow microenvironment.
In these cells, the virus appears to crank out its own version of a human protein called interleukin-6 (Il-6) that is known to stimulate myeloma cell growth. This, the researchers propose, is what propels the runaway growth of myeloma tumors, or as Berenson describes it, "The soil, the dendritic cell, is putting out a bunch of fertilizer, and that makes the seed, the tumor cell, germinate." That kind of remote control, says Yuan Chang, who studies KSHV at Columbia University in New York City, is a "novel mechanism" for virally caused cancer. "This is really exciting, if [the authors] are right."
Drugs to block Il-6 might be one therapeutic avenue, and Berenson also suggests that it might be possible to devise therapies that specifically target the virus-infected dendritic cells themselves. Attacking the virus with drugs or a vaccine might also stave off full-blown multiple myeloma in the estimated 1 million people who have been diagnosed with an apparent precursor condition called monoclonal gammopathy of undetermined significance. Others who might benefit are AIDS patients, especially homosexual men, who have a high risk of becoming infected with KSHV and getting Kaposi's sarcoma.