Identifying a deadly combination of mutations
Exploring how additional genetic changes acquired during a person’s lifetime can work alongside inherited changes to drive AML, Dr Loke is hoping to identify which combinations of mutations are most harmful.
Dr Shaun Patterson at the University of Glasgow is investigating a genetic mutation found in some patients with CML that is linked to disease relapse. His research is exploring how this mutation affects B–cells and whether this may impair the body’s ability to fight AML and what effects this has on disease development.
The Challenge:
As people get older, the blood cells age too. As over the years the body continuously copies DNA in order to replicate blood cells, through time mutations can arise – small mistakes in the genetic copies. Some are harmless, but some can result in cancer. One type is a blood cancer called acute myeloid leukaemia (AML).
The genetic change of interest to Dr Patterson is within the mutated DNMT3A gene – a mutation found in some leukaemia cells. Previously mutated DNMT3A has been linked to changes in the immune system in people with chronic myeloid leukaemia (CML). More specifically Dr Patterson’s previous research found that changes in certain B-cells were associated with relapsed cases of CML when treatment was stopped. This has raised an important question: could DNMT3A mutations also affect B-cells in other blood cancers, such as AML?
B-cells are an important part of our immune system. They help protect us from infections and may also play a role in protecting against cancer. Dr Patterson believes that changes in the DNMT3A gene may interfere with how B-cells work, making it harder for the immune system to recognise and fight cancers such as AML.
The Research:
While research already tells us that some people with AML have changes in the DNMT3A gene, we don’t yet fully understand how these changes contribute to leukaemia.
This project will explore whether DNMT3A mutations affect B-cells. Dr Patterson and colleagues will study B-cells from blood samples donated by people with AML, comparing cells with and without DNMT3A mutations to see how they behave differently.
They will then use laboratory models to test whether changing or blocking these B-cells affects the development of leukaemia. They will also test whether medicines that target B-cells could prevent or slow leukaemia growth and development.
Project information
What difference will this research make?
By understanding the relationship between DNMT3A, B-cells and AML, Dr Patterson hopes to uncover new clues about how the disease develops and identify potential new approaches for preventing or treating AML. These findings could also highlight existing medicines that could be investigated as future treatments for people with AML.
Ultimately, this research could help identify new ways to predict, prevent or treat AML in the future.
