The role of maternal folate in childhood leukaemia initiation; understanding the molecular mechanisms
Leukaemia, a cancer of the blood, is the most common childhood cancer worldwide, responsible for 1 in 3 childhood cancers, and rates are slowly increasing. While survival is high, survivors have many long-term health conditions and reduced life-expectancy.
Folate is a B-vitamin found in green leafy vegetables and liver. Some studies suggest folic acid (the man-made form of folate) supplementation during pregnancy may help prevent childhood leukaemia; however, findings are not yet clear.
Investigating how maternal folate levels contribute to childhood leukaemia would provide further evidence of this relationship. Changes to our genetic code, including swapping round of genetic material called ‘translocations’, can be the first trigger in developing leukaemia. However, the causes of these triggers are unknown.
Moreover, on their own, these triggers are not enough to cause leukaemia, with additional change needed. Changes involving chemical marks that can switch genes on/off, also contribute to leukaemia development.
It’s possible that maternal folate levels affect both the initial triggers and chemical marks that are thought to lead to leukaemia.
Aims and Objectives
The aim of the project is to address a knowledge gap in understanding how maternal folate levels may influence triggers and chemical marks needed for childhood leukaemia development.
We’ll therefore study the influence of folate on these leukaemia triggers and chemical marks.
How it will be done
We will use mouse studies and human cells to investigate the effect of folate on these genetic triggers and chemical marks. We will look for these in a mouse model of folate depletion during pregnancy.
Stored samples are available from developing (unborn) and young mice born to mothers fed low or normal folate diets, in which we will look for these triggers and chemical marks to see if the mothers’ folate levels can produce these in the offspring.
Using state-of-the-art methods, we are able to grow human blood cells in the laboratory in an environment that copies the bone marrow where blood cells develop in the human body. These new methods are more accurate in helping us understand how leukaemia develops.
We will use these methods to treat human blood cells with different amounts and types of folate and look for the triggers and chemical marks that lead to leukaemia. This will help us understand the amount and type of folate that might be needed to prevent leukaemia developing.
Understanding the factors contributing to leukaemia is likely to help refine advice regarding ideal levels of folate intake during pregnancy to reduce risk of childhood leukaemia.
Moreover, this study has the potential to provide biological markers that could be developed to screen or monitor children who naturally have a higher risk of developing leukaemia. This would lead to earlier diagnosis, which is linked to better outcomes for leukaemia patients.
Evidence suggests maternal folate status during pregnancy may influence risk of childhood leukaemia in children, however, the mechanisms through which this relationship exist are unknown. We’d like to thank World Cancer Research Fund in supporting our research to help us investigate how maternal folate levels may influence the molecular triggers involved in the initiation of childhood leukemia development.
Understanding how maternal folate may contribute to childhood leukemia development could lead to refinement of advice to women during pregnancy to prevent childhood leukemia, or the discovery of biomarkers to screen for those children who maybe at higher risk of developing leukemia
Assistant Professor Jill McKay