Michael Caligiuri is associate director for clinical research at Ohio State's Comprehensive Cancer Center

Inflammation may play role in leukemia

An animal study by Ohio State researchers provides new evidence that inflammation may play an important role in the development of certain types of leukemia.

Chemicals known as cytokines are released by cells early in the inflammation response. They are also required for normal immune responses and for the development of immune cells.

"Our findings suggest that cytokines generated by the body during inflammation may be at the heart of certain types of leukemia," said Michael Caligiuri, associate director for clinical research at Ohio State's Comprehensive Cancer Center.

"This is more evidence that inflammation can be a component of cancer. It also provides another reason why nonsteroidal anti-inflammatory drugs are now being tested as possible cancer preventives," he said.

The animal study, conducted by Caligiuri and other researchers, marks the first time that cytokines have been linked to leukemia. It was published in the January issue of the Journal of Experimental Medicine.

The findings, which were made using a new transgenic mouse, suggest that the inappropriate production of cytokines might be an initiating event in some leukemias, "which is not the way we usually think about leukemia," Caligiuri said.

The leukemia that occurred in Caligiuri's transgenic mice closely resembles a human leukemia known as large granule lymphocytic leukemia, or LGL leukemia.

LGL leukemia is a rare leukemia in the United States but common in Japan. The transgenic mouse produced for the study will provide a model that will enable scientists to begin investigating the cause of the malignancy.

Chronic inflammation has in recent years emerged as an important player in the genesis of some cancers. For example, people with pancreatitis, an inflammation of the pancreas, have a higher incidence of pancreatic cancer. And people with Helicobacter pylori infection, which causes a chronic inflammation that leads to ulcers, have a high incidence of lymphoma and stomach cancer, Caligiuri said.

Caligiuri and the team of researchers made their discovery after developing a transgenic mouse in which certain cytokines were produced at much higher than normal levels by cells.

When the mice reached 12 weeks of age, the researchers were surprised to find that about one-third of them began developing leukemia "in a big way," Caligiuri said. These mice had huge increases in white-cell counts, with numbers reaching 100,000 to 600,000 compared to 5,000 in normal control mice.

Furthermore, the cell types that became malignant were quite similar to those in human LGL leukemia. (LGL leukemia is also known as TNK leukemia because it affects a kind of T lymphocyte and NK cells, immune cells that are important in fighting cancers and infectious diseases.) The mice also lost their hair due to the infiltration of leukemic cells into the skin, which is another feature of LGL leukemia.

The researchers are now working to learn what genetic change had occurred to cause the cells in some of the mice to become cancerous. They are also looking at malignant cells from patients with LGL leukemia to learn if those cells have mutations in certain cytokine genes.

In addition, the researchers are using the new transgenic mice to test two agents that might one day be used to treat people with LGL leukemia, which at present is incurable.

Caligiuri's study was funded by grants from the National Cancer Institute.

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One farming practice change makes for cleaner waterways

Changes in farming practices have played a major role in improving water quality in Lake Erie, a recent study suggests. Farm-based pollution has dropped by as much as 50 percent in the region.

D. Lynn Forster, professor of agricultural, environmental and development economics, compared pollutant emissions in 1985 to those 10 years later for two watersheds that drain into the lake. He then compared those results to how farming practices changed in the area during the same time.

Water quality improved with the adoption of farming practices that reduced the amount of fertilizers and chemicals draining from farmers' fields into the lake. The most striking change in farming practices was the rapid adoption of conservation tillage in both watersheds, which more than tripled between 1985 and 1995.

"Farmers in this area began using more conservation practices during the last two decades, which resulted in an overall decrease in agricultural chemicals washing into Lake Erie," Forster said.

www.acs.ohio-state.edu/units/research/archive/waterie.htm