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Researchers Show How Leukemia Develops After Cancer Treatment
Certain Chemotherapy Drugs Damage DNA

2005/05/05

Summary: A team of 20 scientists from the US, England, and France has learned how certain chemotherapy drugs can lead to a particular type of leukemia several years after cancer treatment. The leukemia, called acute promyelocytic leukemia, represents about one-fifth of all leukemias that develop after chemotherapy.They published their findings in the New England Journal of Medicine.

Why it's important: About 1% of cancer survivors treated with chemotherapy will suffer one of its most devastating side effects, acute leukemia. The leukemia usually develops 2-7 years after treatment. Certain types of chemotherapy drugs, including some of those used to treat breast cancer and childhood cancers, are more likely to cause this side effect. Learning how the drugs cause the leukemia may lead to a better understanding of how to prevent it.

What's already known: Like most cancers, leukemia develops because there is an abnormality in the cell's chromosomes, the tiny rod-like structures that contain DNA. DNA is the genetic material that controls all cell processes. Although chromosome abnormalities are found in many types of leukemia, promyelocytic leukemia has a very specific type, called a translocation. In a translocation, part of one chromosome breaks in two and attaches itself to a different chromosome that has also broken. The new chromosomes may begin to make a new protein at the site of the translocation that will cause the cell grow out of control. Promyelocytic leukemia always has a translocation between chromosomes 15 and 17 that seems to cause the leukemia.

How this study was done: The researchers studied DNA from the leukemia cells of 5 patients, of whom 4 had been treated for breast cancer. All had developed promyelocytic leukemia after receiving chemotherapy with either mitoxantrone or doxorubicin. The scientists looked for the break points in DNA from leukemia cells and tried to cause the same break points in normal DNA using the chemotherapy drugs.

What was found: The scientists were able to cause the same breaks in the normal cells by bathing them in one of the drugs and a naturally occurring (and necessary) enzyme called topoisomerase II. Topoisomerase II cuts the DNA so it can unwind and function. Normally, these breaks repair themselves. But the chemotherapy drugs seemed to make the topoisomerase II enzyme work at a super high speed and make many more breaks than could be repaired.

The bottom line: We now know how these particular chemotherapy drugs can lead to leukemia in a small number of people. This study also provides clues about how leukemia develops in people who haven't received any drugs. In the future those clues may lead to new approaches in preventing this disease. The study will also help future investigators learn how other chemotherapy drugs lead to other forms of acute leukemia.

Citation: "DNA topoisomerase II in therapy-related acute promyelocytic leukemia." Published in the New England Journal of Medicine (Vol. 352, No. 15: 1529-1538). First author: Anita Mistry, PhD, Guy's, King's and St. Thomas' School of Medicine, London.

For additional information, please contact:
Cancer Research & Treatment Fund
Phone: 212-288-6604
Fax: 212-288-7704 or 212-746-8246
e-mail: director@crt.org