Penn Medicine News Release
PHILADELPHIA --Mariusz A. Wasik, MD, professor of Pathology and Laboratory Medicine, and Qian Zhang, MD, PhD, research assistant professor, found that a cancer-causing fusion protein works by silencing the tumor suppressor gene IL-2R common gamma-chain (IL-2R?). The results, which appeared in Proceedings of the National Academy of Sciences, suggest new targets for lymphoma and other types of cancer.
Fusion proteins are created by two genes -- originally coding for separate proteins -- joining together. Translation of the fusion gene into an active protein results in a molecule with properties derived from each of the originals. Fusion proteins are relatively commonly found in cancer cells.
The team looked at a fusion protein called NPM-ALK. Anaplastic lymphoma kinase (ALK), which physiologically is expressed only by neurons in fetal life, causes cancer when it is mistakenly expressed in non-neural tissues as a fusion protein with nucleophosphin (NPM) and other partners. NPM-ALK works by silencing the tumor suppressor gene IL-2R?. The ALK fusion genes are active in several cancer types including some carcinomas of the lung, thyroid, and kidney.
The protein IL-2R? is shared by receptors for several proteins called cytokines that play key roles in the maturation and growth of normal immune cells called CD4+ T cells. The Penn team found that IL-2R? expression is inhibited in T-cell lymphoma cells expressing NPM-ALK as a result of epigenetic silencing. The IL-2R? gene promoter is silenced by a chemical change to the DNA itself, in this case, the adding of a methyl group to DNA's molecular backbone... Read More