AIDS-Associated Virus Is Tied to a Common Blood Cancer
By LAWRENCE K. ALTMAN
Published: June 20, 1997
In a surprising finding that is likely to intensify the hunt for viruses as causes of cancer, scientists in Los Angeles have linked an AIDS-associated virus with a common blood cancer.
The virus, Kaposi's sarcoma herpes virus, was discovered in 1994 among individuals who had AIDS and Kaposi's, a cancer that affects the skin and internal organs. In the new study, the virus was linked to multiple myeloma, the second most common blood cancer in this country, after non-Hodgkins lymphoma.
The Kaposi's virus was found in all 15 myeloma patients tested but not in 16 patients with other cancers and 10 healthy volunteers, the authors said in a report being published today in the journal Science. The virus was also detected in patients with two related, but less common blood disorders, Waldenstrom's and amyloidosis, Dr. James R. Berenson, a co-author, said in an interview.
To their surprise, the scientists found the Kaposi virus only in noncancerous cells and not in the malignant myeloma ones. The Los Angeles team suspects that the Kaposi's sarcoma virus may cause myeloma indirectly by the infected cells chemically stimulating other cells to become malignant.
Infection seemed to be limited to the dendritic cells that help provide structure to the bone marrow, said Dr. Berenson's team from the Veterans Affairs Medical Center in Los Angeles and the University of California at Los Angeles.
The study was too limited in scope to prove that Kaposi's sarcoma virus causes myeloma. Much more research would be required to make that case and to learn how the Kaposi's sarcoma virus is transmitted.
Nevertheless, scientists who did not take part in this study said in interviews that the unexpected finding would lead them to widen their search for viruses in other cancers.
While Kaposi's has occurred commonly among men with AIDS, the incidence of myeloma has increased only slightly, possibly because AIDS patients have not lived long enough to develop it.
The findings also have important implications for myeloma. Evidence that the Kaposi's sarcoma virus plays a major role in it could lead to new therapies aimed at the virus, not the cancerous cells. And the findings raise a theoretical possibility of developing a vaccine to prevent myeloma, the authors said.
''It is a solid and fascinating paper,'' said Dr. Anthony S. Fauci, who heads the National Institute of Allergy and Infectious Diseases. ''It should be pursued not only for myeloma but for its implications for other tumors.''
But Dr. Fauci and other scientists cautioned that confirmation would be needed to clarify issues about techniques used in the study and because of the small number of patients involved in it.
Multiple myeloma can produce holes in many areas in bone, causing fractures. It can also produce anemia, profound suppression of the immune system, kidney failure, and leave an individual susceptible to recurrent bacterial infections. Each year, more than 13,000 Americans develop myeloma and 9,000 die from it. For unknown reasons, multiple myeloma occurs about twice as often among blacks as whites.
In addition, about one million Americans develop an abnormal immune globulin in their blood from a condition known as monoclonal gammopathy of undetermined significance, or M.G.U.S. Though the condition generally produces no symptoms and is usually not treated, doctors monitor such patients carefully because about 16 percent of them go on to develop multiple myeloma, sometimes 30 or more years after M.G.U.S. is first detected.
The Los Angeles scientists found the Kaposi's sarcoma virus in two of eight patients with the gammopathy condition.
The new findings grew out of the team's earlier studies on the cancer. And, like many other medical discoveries, it involved a bit of luck.
At a lecture last October, Dr. Matthew B. Rettig, a co-author, learned that the AIDS virus produced a cytokine, or natural chemical of cells, known as IL-6 for interleukin-6. That rang a mental bell. Dr. Rettig knew that IL-6 was essential for the growth and survival of myeloma cells, and that the two other rare cancers in which Kaposi's sarcoma virus had been detected also depended on IL-6 for growth.
''So we immediately started studying the myeloma cells that we had stored,'' Dr. Rettig said.
But they did not find the virus in the myeloma cells of 23 patients. Unknown to Dr. Rettig's team, colleagues at the University of California at Los Angeles and elsewhere in the United States and Europe had looked for the Kaposi's virus in myeloma cells and had not found it.
''If we had known that, we probably would never have pursued this project,'' Dr. Berenson said.
His team knew that the structural tissue known as stroma in myeloma produced IL-6. Dr. Rettig told laboratory assistants to grow cells from samples of bone marrow without adding steroids to the culture fluid, as is usually done, because he thought the steroids might impair the measurements of IL-6.
Dr. Rettig said he recalled the day last December when he found evidence of the virus in stromal cells from the first four patients tested. ''We were shocked,'' he said.
Identifying the infected noncancerous cells specifically as dendritic cells came later. Dendritic cells can extend to reach more than a dozen other cells. ''They probably touch every cell in the marrow and communicate with all the marrow components,'' Dr. Berenson said.
Scientists have noted other links between viruses and cancers. One is hepatitis B and liver cancer. Another is the Epstein-Barr virus, which has been linked to cancers of the nose and throat and certain cancers of the lymph system. Epstein-Barr virus has also been found in noncancerous cells of the mouth and throat as well as in the cancer, said Dr. George Miller, a virologist who made the findings at Yale University.
Because it would be unethical to inject humans with a virus to prove that it can cause cancer, scientists will have to conduct a variety of animal and human studies to prove a viral cause of myeloma.
To determine whether the Kaposi's sarcoma virus transforms M.G.U.S. to myeloma, the scientists plan to test tissues from a larger number of M.G.U.S. patients.