Genetic mutation
Acute leukaemia begins with an alteration to the structure of deoxyribonucleic acid (DNA) that is found in the stem cells that are responsible for producing white blood cells. This is known as a genetic mutation. The DNA provides the cells with a basic set of instructions, such as when to grow and reproduce.
The mutation in the DNA changes these instructions so that stem cells produce more white blood cells than are needed. The white blood cells are also produced when they are still immature so they do not have the infection-fighting properties of healthy ‘adult’ white blood cells.
The number of immature cells (blast cells) increases rapidly, leading to a corresponding decrease in red blood cells and platelets. This reduction in other types of healthy blood cells causes many of the symptoms of acute leukaemia.
It is not known what triggers the condition's development and causes the initial mutation to occur in the stem cells. Most experts believe that the likely triggers of childhood acute leukaemia differ from those of adult acute leukaemia.
Possible triggers of childhood leukaemia
It is thought that around 5% of childhood acute leukaemia cases are caused by related genetic disorders. For example, rates of leukaemia tend to be higher in children with Down’s syndrome (a genetic condition that affects normal physical development and causes mild to moderate learning difficulties).
Exposure to radiation, either before birth or afterwards, is a known risk factor. However, it would require a significant level of radiation, such as the amount released during the nuclear reactor accident at Chernobyl. Due to the potential risk of radiation to unborn babies, medical techniques and equipment that use radiation, such as X-rays, are rarely used on pregnant women.
Most cases of childhood leukaemia occur in children with no history of genetic disorders or exposure to radiation.
The two-hit theory
Most experts support what is sometimes referred to as the "two-hit" theory of childhood leukaemia.
The "two-hit" theory argues that a small number of children are born with a pre-existing vulnerability to developing acute leukaemia, such as a genetic mutation.
However, the theory suggests that they will remain healthy unless they are exposed to a second environmental trigger (hit) and it is this that is required for the condition to develop. Many researchers believe that the second trigger is linked to an infection during childhood.
The possible role of infection
One theory argues that children who have a pre-existing vulnerability to developing acute leukaemia, and are not exposed to infection at an early age, may develop an immature immune system. When their immune system finally meets an infection, it somehow malfunctions and causes a mutation in the stem cells to occur.
The evidence to support this theory is that children who attend playgroups at an early age are less likely to develop acute leukaemia compared with those who do not attend playgroups when they are very young.
Children who mix with others from an early age are exposed to common childhood infections that activate and strengthen their immune systems, making them more resilient to any subsequent infections.
An alternative theory is that that leukaemia may be the result of an increase in the mixing of different populations. For example, when people move from different parts of the country and go to live in a new town.
This may expose children with the pre-existing vulnerability to developing acute leukaemia to infections that their immune system has not learnt to recognise or deal with. This may trigger a similar malfunction and cause a mutation in the stem cells.
The evidence for this is that clusters of leukaemia cases have been recorded near large-scale building projects where families from across the UK are congregated in one place.
However, these theories are not suggesting that leukaemia is infectious, but that it is caused by a rare reaction to infection.
Possible environmental factors
Experts have also carried out extensive research in order to determine whether the following environmental factors could be a trigger for leukaemia:
- living near a nuclear power station
- living near a power line
- living near a building or facility that releases electro-magnetic radiation, such as a mobile phone mast
At the moment there is no evidence to confirm that any of these environmental factors increases the risk of developing leukaemia.
Possible triggers for adult acute leukaemia
Exposure to the chemical benzene is a known risk factor for adult acute leukaemia. Benzene is found in petrol and is also used in the rubber industry. However, there are strict controls to protect people from prolonged exposure.
Benzene is also found in cigarettes, which could explain why smokers are three times more likely to develop acute leukaemia than non-smokers. People who have had chemotherapy and radiotherapy to treat earlier, unrelated cancers also have an increased risk of developing acute leukaemia.
As with childhood acute leukaemia, exposure to high levels of radiation is also a risk factor. People who spend long periods of time in aeroplanes may also be more at risk because the high altitude provides less protection against the sun’s radiation. However, the risk is only thought to be significant if you have spent at least 5,000 hours flying.