OHSU Cancer Institute researcher discovers what fuels certain cancer mutation

December 10, 2007

ATLANTA- An Oregon Health & Science University Cancer Institute researcher has discovered that a particular hormone is responsible for driving a cancer enzyme to cause an often deadly red blood cell cancer.

Researchers working with the cancer mutation in the JAK2 enzyme have found that the enzyme is dependent on the hormone TNF-alpha to grow and cause a red blood cell cancer called polycythemia vera, said principal investigator Thomas Bumm, M.D., Ph.D., OHSU Cancer Institute member.

This research will be presented at the American Society of Hematology annual meeting in Atlanta on Monday, Dec. 10, at 3:30 p.m.

Polycythemia vera is a disease in which there are too many red blood cells in the bone marrow and blood, causing the blood to thicken. There is no cure.

Mice with normal TNF-alpha production and the JAK2 mutation developed the red blood cell disease very quickly - within two to three weeks. The blood became very thick, and they developed severe bone marrow fibrosis, excessive fibers in the bone marrow with a decrease in healthy cells. In contrast, mice without the hormone but carrying the JAK2 mutation had normal red blood cell levels and normal bone marrow.

The hormone, TNF-alpha is known as a highly potent hormone, but until now its role in cancer has not been well understood.

"If these specific hormones are understood, then there is hope to find a new way to fight these cancer cells by attacking the specific hormones triggering the cancer cells," said Bumm, a fellow in hematology/ medical oncology, OHSU School of Medicine.

There are already drugs developed that target TNF-alpha used for patients with auto immune and inflammatory diseases such as rheumatoid arthritis. But the drugs have not been used for cancer patients. Bumm said one of the next steps will be to conduct studies on a larger mouse study and also testing these different drugs' effect on this JAK2-induced cancer.

"Maybe one of these drugs will work on the mice and is safe so that we could begin testing the drugs on patients. At this point, there is no specific treatment for polycythemia vera cancer patients. Maybe we opened a new door to understand leukemia better and to fight it at a crucial root," Bumm said.

Polycythemia vera is rare, about five in every 1 million people have it. Without treatment, about half the people who have polycythemia vera with symptoms die in less than two years.

Often, people with polycythemia vera have no symptoms for years. The earliest symptoms usually are weakness, fatigue, headache, light-headedness, shortness of breath and night sweats. Vision may be distorted, and a person may have blind spots or may see flashes of light. Bleeding from the gums and more bleeding than would be expected from small cuts are common. The skin, especially the face, may look red. A person may itch all over, particularly after bathing or showering.
-end-
This research is abstract #675.

The OHSU Cancer Institute is the only National Cancer Institute-designated center between Sacramento and Seattle. It comprises some 120 clinical researchers, basic scientists and population scientists who work together to translate scientific discoveries into longer and better lives for Oregon's cancer patients. In the lab, basic scientists examine cancer cells and normal cells to uncover molecular abnormalities that cause the disease. This basic science informs more than 200 clinical trials conducted at the OHSU Cancer Institute.

Oregon Health & Science University

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