Category: Laboratory Research

Researchers Find New Role of Gene that Could Lead to New Strategies for the Treatment of B-Cell Lymphomas

The activation-induced cytidine deaminase (AID) gene has long been understood to play a role in the body’s defense against pathogens. The AID gene ensures that the B-cells responsible for antibody production can generate the antibodies that defend the body. Recently a team of research scientists at Weill Cornell Medical College published results outlining a new role for the AID gene. In these first of their kind findings researchers demonstrated the epigenetic role of the gene:

“…the researchers discovered that the enzyme encoded by the AID gene is also involved in removing chemical tags from DNA. These tags, known as methyl groups, regulate gene expression. Removing these methyl groups, a process called hypomethylation, allows B cells to rapidly change their genome in preparation for antibody production.”

“AID is a gene traditionally not known to be linked to DNA methylation, but we found that it is a player in removing methyl groups — the first time anyone has found molecules that perform this powerful form of gene regulation,” said co-senior author Dr. Olivier Elemento, an associate professor of computational genomics in the Department of Physiology and Biophysics who heads the Laboratory of Cancer Systems Biology in the Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine at Weill Cornell and co-chairs the Meyer Cancer Center Program in Genetics, Epigenetics and Systems Biology. “What is interesting is that many tumor types, and that includes B-cell lymphomas, tend to be linked to global — genome-wide — hypomethylation, compared to normal cells. How hypomethylation occurs is not well understood. AID is so far the only enzyme that has been directly linked to this active process. So AID or related enzymes could be involved in other cancers as well.”

These new findings have the potential to reveal a new cause of blood cancers and lead to the development of new strategies to treat B-cell lymphomas.

Researchers Discover Role of Mutated Gene in Development of non-Hodgkin Lymphomas

Recently researchers from Weill Cornell Medical College and Memorial Sloan Kettering Cancer Center discovered how a mutation in the KMT2D gene can drive the development of certain non-Hodgkin lymphomas. When properly functioning the gene KMT2D allows B-immune cells to generate antibodies against foreign objects in the blood stream. However, genetic mutations can disrupt normal immune cell growth, and prevent the proper functioning B-immune cells. Researchers found that,

“…normally KMT2D prepares key genes to respond to signals from other immune cells that stop B-cells, also called B-lymphocytes, from dividing and cause them to start making antibodies. However, when KMT2D mutations develop in B-cells, these external signals are no longer able to restrain them from dividing and stimulate their production of antibodies. As a result, there is an accumulation of rapidly dividing B-cells that eventually become malignant lymphomas. Importantly, the group demonstrated that therapies that have been developed to kill lymphoma cells by targeting these same signals are ineffective in the presence of KMT2D mutations.”

“KMT2D turns out to be one of the top 20 most mutated genes across all cancer types. It is really one of the superstars of cancer because it is one of the genes that is most strongly linked to tumors,” said co-senior author Dr. Ari Melnick, chair of the hematologic malignancies program in the Sandra and Edward Meyer Cancer Center and the Gebroe Family Professor of Hematology/Oncology at Weill Cornell Medical College. “Now that we understand how the gene functions in this treatment-resistant lymphoma, we can investigate the role of KMT2D mutations in other cancer types.”

These findings could potentially answer the question as to why certain lymphoma sub-types are treatment-resistant, while allowing for new avenues of therapeutic targeting.

Lymphoma Program to Collaborate with Mayo Clinic in Nationwide, Multi-Instutional Grant on Survivorship in Non-Hodgkin Lymphoma

Last week the Mayo Clinic received an $11 million grant from the National Cancer Institute (NCI) to support research addressing the current and long-term unmet healthcare needs of patients with non-Hodgkin lymphoma. This NCI funded, multi-institutional project is known as the “Lymphoma Epidemiology of Outcomes Cohort Study”. At the Weill Cornell site, Dr. Peter Martin will serve as the Principal Investigator, and Dr. John Leonard will be a participating investigator.

As Principal Investigator at the Weill Cornell site, Dr. Martin, who is the Charles, Lillian, and Betty Neuwirth Clinical Scholar in Oncology, will be overseeing the recruitment of participants and reporting of outcomes. “The LEO Collaboration will be the largest study of it’s kind anywhere in the world and will undoubtedly lead to important, impactful discoveries. We look forward to enrolling participants at Weill Cornell as we seek avenues to increase long-term prognosis and survivorship for those living with NHL,” says Dr. Martin.

Working with participating investigators, Dr. John Leonard and Dr. Giorgio Inghirami (Pathology, Weill Cornell Medical College). “This multi-institutional collaborative study group, supported by the NCI, has a highly productive track record. We are very happy to be a part of it,” says Dr. Leonard.

Look to this space for further information about this study, and other Hodgkin lymphoma related trials. A full listing of our non-Hodgkin lymphoma trials can be found here.