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.