Carl Ware, Ph.D., director of Sanford-Burnham’s Infectious and Inflammatory Disease Center, was recently awarded a new five-year grant from the National Cancer Institute, part of the U.S. National Institutes of Health, to examine how a family of cellular communication proteins—called cytokines—are disrupted in lymphoma and leukemia.
Leukemia and lymphoma are types of blood cancers—they can affect a person’s bone marrow, blood cells, lymph nodes, or other parts of the lymphatic system. According to the Leukemia & Lymphoma Society, one person in the U.S. is diagnosed with a blood cancer approximately every four minutes. While the survival rate for people with leukemia and lymphoma has increased in recent years due to research and new treatments, approximately 53,000 Americans died from these cancers in 2011.
Cytokines normally control the growth of white blood cells—immune cells that help the body fight infection. Two genes that encode cytokines—HVEM and BTLA—are frequently mutated in human lymphomas. The prognosis is worse for patients with these mutations. Researchers in Ware’s laboratory recently found new evidence that HVEM mutations in human lymphomas specifically alter cytokine function, wreaking havoc on cellular survival pathways and the immune system.
“This grant will allow us to explore how specific genetic changes—mutations—in cytokine genes contribute to the development of lymphoma,” Ware said. “The cytokine gene we study, known as HVEM, is frequently mutated in cancers, particularly in follicular lymphoma. Our previous studies indicate that HVEM is important for regulating the immune defense against viruses. Now, we hypothesize that genetic changes in HVEM are not random, but specifically selected for—that they allow the cancer cell to evade immune controls. Understanding the nature of these mutations may allow us to design drugs that restore immune control of the lymphoma cell.
In this newest project, the team will further unravel the mechanisms behind HVEM and BTLA malfunction in human lymphoma cells. They will also examine the HVEM-BTLA system in mouse lymphoma models and use an array of molecules that can boost or block HVEM and BTLA cytokines to further probe their functions.
Ware and his team will also determine whether potential drugs directed at these cytokines can help stop the growth of lymphoma and leukemia.
“Ultimately, we hope these studies will provide the rationale to therapeutically manipulate these pathways as a method to treat leukemia, lymphoma, and related blood cancers,” Ware said. “We’re thankful to the NIH for giving us the opportunity to pursue these ideas… and hopefully to save lives.”