|New understanding of cell metabolism yields promising target for new lymphoma therapies|
|July 03, 2012|
A research team led by scientists at The University of North Carolina at Chapel Hill has found that two interrelated metabolic processes - involving sugar utilization and fatty acid synthesis - contribute to cell proliferation in non-Hodgkin lymphoma, a cancer of the white blood cells.
The finding is significant in that it opens the door to targeted treatments for the disease in lieu of more dramatic treatments, up to and including bone marrow transplant.
Co-authors of the study, which appeared online July 2 in Proceedings of the National Academy of Sciences, include UNC Gillings School of Global Public Health nutrition researchers Liza Makowski, PhD, assistant professor, and Alex Freemerman, PhD, research associate.
Lymphocytes, immune system cells that help the body fight infection, can be one of two main types - B or T cells. B cells typically help protect the body against bacteria and viruses by making antibodies. T cells can directly destroy infected cells. Either type of lymphocyte can be involved in lymphoma, and treatment for the lymphoma is dependent upon which type of cell is involved.
Blossom Damania, PhD, professor of microbiology and immunology in the UNC School of Medicine and the study's lead author, has investigated various types of non-Hodgkin lymphoma, some of which can be associated with viral infection. She and colleagues have shown that a particular cell signaling pathway (PI3K/AKT/mTOR) is activated in several types of B-cell non-Hodgkin lymphoma (B-NHL).
Cell signaling is part of a complex communications system that coordinates the activity of cells and allows them to repair tissue and develop immunities. When the cell communications system goes awry, diseases such as cancer or diabetes can result.
The cell signaling pathway is also important in controlling cell metabolism, including how the cell utilizes glucose (sugars) through a process called aerobic glycolysis, and how it makes fatty acids for the purpose of cell replication.
"Our team found evidence that glycolysis and fatty acid synthesis are interdependent in B-NHL," Damania said. "The good news is that the lymphoma cells are much more sensitive to a compound that inhibits fatty acid synthesis, as compared to normal B cells. This suggests that fatty acid synthase, the enzyme that drive fatty acid synthesis, is a promising target for new therapies against lymphoma."
Aadra Bhatt, a graduate student in the department of microbiology and immunology and a member of UNC Lineberger, was first author of the study. Other members of the research team include Dirk Dittmer, PhD, also a UNC Lineberger member and professor of microbiology and immunology in the School of Medicine; Sarah Jacobs, PhD, postdoctoral fellow at the UNC cancer center; and Jeffrey Rathmell, PhD, associate professor of pharmacology and immunology at Duke University.
The project was funded by grants from the National Institutes of Health, the National Cancer Institute and the University of North Carolina University Cancer Research Fund.
Damania, a member of UNC Lineberger Comprehensive Cancer Center, is a Leukemia and Lymphoma Society Scholar and a Burroughs Wellcome Fund Investigator in Infectious Diseases.
|Last updated July 03, 2012|