Researchers Find Possible Cure For Type of Leukemia

Harvard researchers at Brigham and Women’s Hospital have discovered a potential cure to one of the most prevalent types of leukemia found in children and adolescents.

Drugs currently being developed to treat Alzheimer’s may also put a common type of childhood leukemia—T-cell acute lymphocytic leukemia—into remission, said Jon C. Aster, an associate professor of pathology at Harvard Medical School (HMS) and the leader of the study.

The study was published Friday in the journal Science.

This treatment promises to be more effective than the current approaches, and also more gentle to the patient, he said.

Current methods of treating T-cell acute lymphocytic leukemia include a combination of chemotherapy drugs which are highly toxic not only to cancer cells, but also to healthy cells. Even then, approximately one quarter of patients experience relapse.

“We think [our therapy] is better because it’s more specific and thus less toxic,” said Aster.

Michael A. Gimbrone Jr., chairman of the hospital’s Department of Pathology and Friedman professor of pathology at HMS, was excited about the prospects for timely treatment.

“This points the way to early diagnosis, more effective treatment and ultimately prevention,” he said.

Leukemia is a rapid-progressing cancer of white blood cells, and this particular type affects more than 600 children annually.

“It’s a very aggressive disease because the tumor cells replace normal cells on the bone marrow,” said Aster. “Kids have low blood counts, anemia, not enough white blood cells and sometimes also tumor masses.”

In the study, Aster and his co-workers have discovered a common mutation in a gene called NOTCH1 in 55 to 60 percent of all T-cell acute lymphocytic leukemia patients.

“That’s a substantially higher number than any other mutation found in the cancer,” said Aster.

According to Aster, normal NOTCH1 gene activity is essential for T-cells, which defend the body against disease, to mature. The NOTCH1 gene is mediated by a critical molecule called gamma secretase.

In patients with T-cell acute lymphocytic leukemia, the NOTCH1 gene is mutated and gamma secretase keeps the gene turned on, leading to T-cell overproduction and eventually leukemia.

According to Aster, stopping the effects of the gamma secretase would bypass NOTCH1’s abnormal activity, thus stopping the cancer from progressing.

Drug companies are now developing gamma secretase inhibitors in an effort to help Alzheimer’s patients.

“Gamma secretase inhibitors are not yet on the market,” said Aster. “However, several colleagues of mine informed me that gamma secretase inhibitors were being developed in major pharmaceutical companies.”

Clinical trials are slated to begin within the next few months, in collaboration with the Dana-Farber Cancer Institute and Brigham and Women’s Hospital researchers.

In the meantime, scientists are studying the NOTCH1 gene and its role in leukemia.

“We want to understand the basic events in NOTCH1 signalling,” said Stephen Blacklow, associate professor of pathology at HMS and co-author of the study. “Hopefully this will lead to the discovery of broad-based mutations underlying all cancers.”

—Staff writer Risheng Xu may be reached at xu4@fas.harvard.edu.