Los Angeles Times (Home Edition) Friday June 20, 1997 Page B-1
Thomas H. Maugh II; Times Medical Writer

Although it is rare in the public at large, the recently discovered virus is relatively common among people with the human immunodeficiency virus that causes AIDS. And at least some researchers fear an increase in multiple myeloma as HIV patients survive longer from new drug treatments.

Multiple myeloma, not spread through casual contact, now afflicts an estimated 50,000 Americans, striking about 15,000 each year. It is the second most common cancer of the blood.

Although a vaccine for the cancer is many years away, Dr. James R. Berenson, lead author of the VA study published today in Science, and his colleagues are testing new therapies based on the virus' involvement.

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"We now have a new target for developing treatments and possibly a vaccine to prevent multiple myeloma," Berenson said.

"This is really exciting if they are right," said molecular biologist Yuan Chang of Columbia University, who first suggested the virus' existence.

The new virus, called Kaposi's sarcoma-associated herpesvirus, or KSHV, is not the first virus shown to cause cancer in humans. Scientists now estimate that 15% to 20% of human cancers are viral in origin. Examples of cancer-causing viruses include the human papilloma virus, which can cause cervical cancer, and Epstein-Barr virus, which can cause a form of lymphoma.

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Berenson emphasized that neither multiple myeloma nor any other cancer is contagious in the conventional sense. A viral infection is necessary for the cancer to occur, but it is not sufficient, he said. Other factors also contribute to the formation of a tumor.

In multiple myeloma, malignant cells accumulate in bones, blood and the kidneys, producing intense pain and damage that generally proves fatal. It is normally treated with chemotherapy, but the average survival period after diagnosis is only about 30 months.

Other researchers have looked for KSHV in multiple myeloma cells, which arise from plasma cells in the bone marrow, but have not found it. Neither, in fact, did Berenson and his associates, including Matthew B. Rettig of the VA center and Jonathan W. Said of UCLA's Jonsson Comprehensive Cancer Center.

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But the VA team went one step further and looked in the supporting cells, called dendrites, that surround the plasma cells in the marrow and provide nourishment. They found the virus there "in every single [myeloma] patient," Berenson said.

The virus was not present in dendritic cells from healthy people or patients with other types of cancer.

"That's pretty compelling evidence," said Dr. Jay A. Levy of UC San Francisco.

Exploring further, they found that KSHV has a unique mechanism among cancer-causing viruses--in effect, producing cancer by remote control.

Researchers already knew that the growth of multiple myeloma is spurred by a naturally occurring chemical called interleukin -6, or IL-6, a component of the immune system that is also important in bone metabolism.

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The VA team found that the virus produces its own version of IL-6 that sharply stimulates growth of the malignant cells. In that sense, the virus does not actually cause the cancer--which may be triggered by a genetic defect--but the cancer apparently cannot grow without its presence.

Support for that idea comes from studies of a little-known condition called "monoclonal gammopathy of undetermined significance," which affects an estimated 1 million Americans. This condition appears to be basically harmless and can be identified only by a blood test, but 25% of the people with the condition go on to develop multiple myeloma over about 10 years.

Berenson and his colleagues have tested several people with monoclonal gammopathy and have found, coincidentally, that about 25% of them are infected with KSHV. The team is trying to determine if the infected individuals are, in fact, the patients who go on to develop cancer.

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Meanwhile, the researchers are attempting new treatments based on their discovery.

Normally, Berenson said, multiple myeloma patients in the earliest stages of the disease are not treated with chemotherapy because it provides no benefit. The team is giving these patients antiviral drugs known to affect other herpes viruses in the hope that this will slow progression of the cancer. None has been treated long enough to judge results, however.

Berenson is also testing a device manufactured by Cell-Pro Inc. of Seattle that removes myeloma cells from bone marrow. He has found that the device also removes dendritic cells infected by the virus, which may retard growth of the cancer.

Further in the future, he hopes to develop drugs that will block the action of IL-6, and perhaps a vaccine that could be given to monoclonal gammopathy patients to prevent progression to multiple myeloma.

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