Studies of rare blood syndrome yield novel route to cancer

tyrosine kinases is unregulated which can occur when chromosomes improperly exchange chunks of genetic material, creating chromosomal rearrangements cancer may develop.

With the apparent successes reported in the initial small case studies, Gilliland, Stone and their colleagues decided to conduct their own clinical trial and attempt a detailed study that they hoped would reveal the underlying mechanism of HES. They enlisted the aid of colleagues at eight medical centers who contributed 11 patients to the study.

"Nine of the eleven patients showed extraordinary and continuing responses to Gleevec treatment," said Gilliland. "Their eosinophilia just went away. In one case, a patient with severe involvement of his central nervous system, in which he had lost bowel and bladder function, completely recovered. It's stunning to see such a recovery due to a simple pill that has minimal side effects compared to conventional chemotherapy."

According to Gilliland, the initial group of patients is still responding to the drug, as have additional patients recruited after submission of the New England Journal of Medicine article. In an interesting twist, the researchers found that they could successfully treat HES patients with doses of Gleevec that were lower than those used to treat patients with chronic myelogenous leukemia. This is significant, Gilliland said, in part, because Gleevec is very expensive.

In the laboratory, the difficult work began when Gilliland and his colleagues tried to find a molecular explanation for why the patients responded to Gleevec therapy. "We didn't have any clues where to look," Gilliland said. "This is not an inherited disease, so you cannot use the same strategies that one would use in familial breast or colon cancer. There are no recurring chromosome abnormalities that could reveal an underlying cause."

Careful genetic analysis by Cools revealed some interesting information: His work showed tha

Contact: Jim Keeley
Howard Hughes Medical Institute

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