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.

A Road Map for Discovery and Translation in Lymphoma

In August 2014 the American Society of Hematology (ASH) organized the inaugural Meeting on Lymphoma Biology. The meeting’s Steering Committee was tasked with recommending a road map for future priorities in lymphoma discovery and translation. After identifying roadblocks that limit research they made recommendations on how to supersede them in the future. According to their recommendations:

The road map is based on the fundamental goal of extending effective treatment to all patients with lymphoma. Achieving that goal with maximum efficiency and expedience will require a broad and collaborative effort between researchers, patients, funding agencies, pharma, and advocacy groups.

Among the members of the distinguished committee, Weill Cornell Medical College was represented by Lymphoma Program Director, Dr. John P. Leonard and Dr. Ari Melnick, Chair of the Hematologic Malignancies Program at the Sandra and Edward Meyer Cancer Center.

The Precision Medicine Approach at WCMC Explained

In a recent article from the The Magazine of Weill Cornell Medical College and Weill Cornell Graduate School of Medical Sciences, physicians and scientists from the Lymphoma Program explained their approach to treating lymphoma. Dr. John Leonard explained,

“You shouldn’t treat everybody who walks in the door the same way. We want to treat with a tailored approach based on what’s most likely to work for that individual patient.”

Blood cancers have been at the forefront of research on tailored approaches to treatment, known as precision medicine. In large measure, these advancements are due to researchers’ ability to access tumor material from such patients more readily than they can with other types of cancer. In the past decade, Weill Cornell researchers have been involved in developing or testing almost every new lymphoma drug recently approved by the FDA. While most cancers today are treated primarily through surgery and radiation, Leonard notes, cancers of the blood are different. “Lymphoma is a disease where treating with drugs is central to curing the patient,” he says.

The entire article can be read here.