BOSTON - In the process of figuring out why an anti-cancer drug is effective in treating patients with a rare blood disorder known as hypereosinophilic syndrome, or HES, researchers at Brigham and Women's Hospital (BWH) and the Dana-Farber Cancer Institute have shown that the condition may in fact be a form of cancer.
Their findings appear in the March 27 issue of the New England Journal of Medicine.
HES develops when the level of eosinophils, a white blood cell, rises to abnormal levels in the bloodstream. Sometimes the body produces large amounts of eosinophils as a reaction to allergies or parasites, but why eosinophil levels increase in those patients with HES has remained elusive, until now. Elevated eosinophil levels can lead to heart failure and negatively impact other vital organs, often leading to death.
Imatinib (tradename Gleevec), a drug that has already shown promise in the treatment of chronic myelogenous leukemia, or CML, a form of cancer that involves the overabundance of another kind of white blood cell, was used by Dana-Farber's Daniel DeAngelo, MD, PhD, and Richard Stone, MD, to treat patients with HES. The idea to use this drug derived from both a notion that the mechanism of HES might be similar to CML as well as early reports, ultimately published in the journal Lancet in May 2002, of its utility in HES. The HES patients at DFCI, including one who was very ill, responded extremely well to the drug, although exactly how the drug kept the otherwise aggressive disease at bay was unclear.
"Our research addresses the question of why patients with HES respond so well to imatinib," said Gary Gilliland, MD, PhD, of BWH, who is senior author of the paper with Stone. "We have shown that a small deletion of DNA in the blood cells of HES patients fuses two genes together, creating a novel cancer-causing gene that is inhibited by imatinib. This fusion explains the clinical response these patients have to imatinib, and demonstrates that HES is a form of cancer."
HES is a rare disorder, occurring in less than one in every 100,000 people per year. It almost always affects men. Stone and Gilliland that the rarity of the condition does not dilute the broader implications of the findings.
"The creation of a cancer-causing gene by a small deletion of DNA is a novel genetic mechanism that may be present in many other tumors if we look for it," said Stone. "As we learn more about the genetics of cancer, we should be able to develop other targeted therapies like imatinib."
In January, researchers at BWH, Dana-Farber, and the Oregon Health Sciences University used their knowledge that c-kit, which is related to the critical protein in HES, was mutated in a certain kind of stomach cancer (gastrointestinal stromal cell tumor or GIST) and showed that patients with this aggressive disease could dramatically respond to imatinib. Stone and Gilliland – who are both professors at Harvard Medical School – characterized this effort as "a perfect example of 'bedside to bench' research" as clinical and laboratory scientists at BWH and Dana-Farber worked side by side. The researchers say this discovery has the potential to be brought back to the bedside to help patients with other types of cancers.
The study was supported in part by the National Institutes of Health, the Leukemia and Lymphoma Society, Fonds voor Wetenschapdelijk Onderzoek-Vlaanderen, and the Belgian American Educational Foundation.
BWH is a 716-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare System, an integrated health care delivery network. Internationally recognized as a leading academic health care institution, BWH is committed to excellence in patient care, medical research, and the training and education of health care professionals. The hospital's preeminence in all aspects of clinical care is coupled with its strength in medical research. A leading recipient of research grants from the National Institutes of Health, BWH conducts internationally acclaimed clinical, basic and epidemiological studies.
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), a designated comprehensive cancer center by the National Cancer Institute.
The above post is reprinted from materials provided by Dana-Farber Cancer Institute. Note: Materials may be edited for content and length.
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