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Hormone Control Of Rare Leukemia Sheds Light On Molecular Basis Of Cancer

Often in science it's the exception that illuminates the rule. Thus, when researchers at the University of Pennsylvania Medical Center clarified the biochemical mechanism behind acute promyelocytic leukemia (APL), they simultaneously elucidated a process implicated in many other cancers. APL is a bone marrow cancer that strikes about 3,000 people in the United States every year.

"This study gets at the exact biochemical and genetic cause of the uncontrolled cell growth in this leukemia," says Mitchell A. Lazar, MD, PhD, chief of the division of endocrinology, diabetes, and metabolism. "Understanding the molecular basis of this disease will teach us important lessons about cancer in general." Penn researchers and colleagues from the European Institute of Oncology in Milan report their findings in the February 19 issue of Nature.

The genetic mistake that makes APL so deadly is a translocation between two chromosomes. These chromosomes break and fuse together again during cellular division, resulting in a new gene with material from each. The protein encoded by the new gene is called a fusion protein. Chromosomal translocations figure in many types of cancers.

In 95 percent of APL cases, the fusion protein is a product of a gene called PML on chromosome 15 and the gene for the retinoic acid receptor (RAR) on chromosome 17. In another 4 percent of the cases, the protein is a fusion between the RAR and a gene for a protein of unknown function called PLZF.

"The involvement of the retinoic acid receptor in both forms of APL is key to understanding the complex genetics of this disease," says Lazar. The receptor is regulated by vitamin A, which is converted to the gene-controlling hormone retinoic acid once in the body. "Interestingly, a few years ago, researchers discovered that a Chinese herbal remedy was curing most of the APL cases in which it was used,
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Contact: Karen Young Kreeger
kreeger@mail.med.upenn.edu
215-662-2560
University of Pennsylvania School of Medicine
18-Feb-1998


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