Modification of Fusion Protein Causes Blood Cancers

Modification of Fusion Protein Causes Blood Cancers

Lan Wang, Ph.D., an Empire State Stem Cell Fellow at Memorial Sloan-Kettering Cancer Center, just published new data in Science identifying the mechanism behind the uncontrolled cell proliferation leading to certain blood cancers. Dr. Wang and her mentor, Stephen Nimer, M.D., study the blood cancer acute myelogenous leukemia (AML). Their new research identifies the mechanism by which one of the most common mutations leading to AML can cause uncontrolled cell growth. This mutation fuses two genes, AML1 and ETO, together. AML1 is necessary for development of stem cells that produce blood and ETO acts to repress transcription. However, the fusion product of these two genes is a potent activator of proliferation specifically in these blood stem cells. Drs. Wang and Nimer now show that post-translational acetylation, adding an acetyl group to a specific amino acid in AML1-ETO, is the key to AML1-ETO´s newfound activity. Further, inhibition of this acetylation reduces the growth of cancer cells. This finding presents an attractive target for development of new therapeutics and may be applicable to other types of cancers besides AML as well. This project was supported in part by a NYSTEM Fellow to Faculty award to Dr. Wang (contract #C026720).

Wang L, Gural A, Sun XJ, Zhao X, Perna F, Huang G, Hatlen MA, Vu L, Liu F, Xu H, Asai T, Xu H, Deblasio T, Menendez S, Voza F, Jiang Y, Cole PA, Zhang J, Melnick A, Roeder RG, Nimer SD. The Leukemogenicity of AML1-ETO Is Dependent on Site-Specific Lysine Acetylation. Science. 2011 Aug 5; 333 (6043): 765-769.