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Studies of rare blood syndrome yield novel route to cancer

By carefully studying why a rare blood disorder responds to the anti-cancer drug Gleevec, researchers have discovered an entirely new mechanism that generates cancer-causing genes.

The study, published in the March 27, 2003, issue of the New England Journal of Medicine, shows that Gleevec is an effective treatment for hypereosinophilic syndrome (HES), a blood disorder that is nearly always fatal. According to the researchers, their studies suggest that HES should be reclassified by the World Health Organization from its current "gray-area" status as a "syndrome" to a form of cancer.

Senior authors of the article were D. Gary Gilliland, a Howard Hughes Medical Institute investigator at Brigham and Women's Hospital and Harvard Medical School, and Richard Stone at the Dana-Farber Cancer Institute (DFCI). Joint first authors on the paper were Jan Cools, a postdoctoral fellow in Gilliland's laboratory, and Daniel DeAngelo, who is also at DFCI and an instructor at Harvard Medical School.

HES is caused by overproliferation of a type of white blood cells called eosinophils. Physicians treat the syndrome with a combination of drugs and chemotherapy, said Gilliland, but eventually, the assault of eosinophils damages major organs, and causes the heart or lungs to fail, and ultimately results in death of most patients.

Recently, however, hints that the disorder might respond to Gleevec began to crop up in the medical literature. "There was a report of a single case of an HES patient treated with Gleevec and had what was described as a miraculous response," said Gilliland. "This anecdotal report was substantiated by a group of investigators that reported successful treatment in 4 of 5 additional HES patients, reported in the The Lancet (a British medical journal) last year.

Gleevec works by inhibiting enzymes called tyrosine kinases. When the activity of
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
26-Mar-2003


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