"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,
Contact: Karen Young Kreeger
University of Pennsylvania School of Medicine