An international collaboration involving researchers from Queen Mary University of London, Memorial Sloan Kettering Cancer Center (MSK), New York and the Dana-Farber Cancer Institute, Boston has secured a $ 1 million research grant from the Dutch Blood Cancer Charitable Association. Lymph & Co., to investigate a new treatment. target for lymphoma.
The aim of the project is to determine how the target of a protein called KDM5 kills lymphoma cells and to identify the groups of patients who are most likely to benefit from this type of treatment.
Lymphoma is a type of blood cancer that arises from white blood cells called lymphocytes. Changes in the genetic code (mutations) of lymphocytes can cause them to grow uncontrollably and, as a result, these white blood cells accumulate in the lymph nodes and other tissues, eventually causing lymphoma. There are two main types of lymphoma: Hodgkin’s lymphoma and non-Hodgkin’s lymphoma (NHL), which include over 60 subtypes.
Fighting the effects of common lymphoma mutations
Research has shown that many lymphoma patients have one or more mutations in a gene called KMT2D. The KMT2D gene encodes a protein involved in controlling gene expression within cells; however, mutations that inhibit the proper functioning of KMT2D (leading to changes in the expression of genes necessary for normal cell function) are the most common mutations detected in lymphoma.
Collaborative teams, led by Professors Jude Fitzgibbon at the Queen Mary’s Barts Cancer Institute (BCI), Hans-Guido Wendel, MD at MSK, and David Weinstock, MD at Dana-Farber, are leaders in the study of lymphomas using cell lines and animal patterns. . Based on recent experiments, researchers believe that the target of a protein – called KDM5 – that normally counteracts the effects of KMT2D could alter the effects of KMT2D mutations on lymphomas, causing lymphoma cell death.
The project will build on previous work by teams, including recent research led by BCI professor Fitzgibbon and former postdoctoral researcher Dr. James Heward, who discovered the inhibition of KDM5 to reverse the effects of KMT2D mutations on cell lines and preclinical patterns of an NHL group. called germinal center lymphomas. It is also based on previous work by the Wendel laboratory that first characterized the role of KMT2D mutations in the development of lymphoma.
Lead researcher from BCI, Professor Fitzgibbon, said: “Thanks to the generous support of Lymph & Co., we have the opportunity to build a unique international collaboration, to build on our groups’ understanding of KMT2D mutations and to determine if the inhibitory power of KDM5 is specific for germ center lymphomas or may have a wider therapeutic potential in other non-Hodgkin lymphomas. “
A precise-medical approach
Much research has focused on what distinguishes one type of lymphoma from another. KMT2D mutations are present in only 5-20% of some lymphoma subtypes, but up to 80% of a lymphoma subtype called follicular lymphoma, which is the second most common lymphoma in the UK, US and Europe. Therefore, teams will investigate whether the goal of KDM5 can be an effective therapeutic approach for a range of lymphoma subtypes. Indeed, KMT2D and related genes have been mutated into many other cancers, so an effective therapeutic target of KDM5 may be widely beneficial to many people with cancer.
If research shows that KDM5-led therapy is effective in compensating for the effects of KMT2D mutations on lymphoma, then the study could provide a new approach to treating lymphoma. As part of the project, the researchers aim to identify KDM5 inhibitors that would be suitable for evaluation as part of early-stage clinical trials and to create populations of patients who are most likely to benefit from these therapies.
Furthermore, by improving their understanding of the harmful effects of KMT2D mutations within lymphocytes, the team seeks to identify other molecules that can be targeted with drugs already approved for clinical use.
Dr. Weinstock, who heads the Lavine family for cancer prevention therapies at Dana-Farber and is a professor of medicine at Harvard Medical School, said: “It is a great honor to be part of this team under the leadership of Dr. Fitzgibbon. “Our goal is to utilize the talent and resources in our research programs to directly target one of the most important changes in follicular lymphoma and other cancers.”
“This is a great time to translate the understanding of cancer mechanisms into new lymphoma therapies.”
Dr. Wendel, Professor, Cancer Biology and Genetics Program, MSK
Prof. Dr. Bob Lowenberg, chairman of the scientific advisory board of Lymph & Co., said: “The aim of Lymph & Co. is to provide leading doctors and scientists researching lymph node cancer with tools that allow them to carry out this research anywhere in the world. Within this unique research project Lymph & Co, an international consortium of top researchers from London, Boston and New York will join forces and have the opportunity to seek better treatment options for patients with common forms of lymph node cancer. these researchers. “
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