Acute Lymphocytic Leukaemia: Peripheral Blood Smear. (Credit: Medical Dictionary, © 2009 Farlex and Partners)

A major new analysis reveals for the first time the likely cause of most cases of childhood leukaemia, and that the disease might be preventable. 

Professor Mel Greaves, from the Institute of Cancer Research, has gathered 30 years of evidence to show that acute lymphoblastic leukaemia (ALL) is caused through a two-step process of genetic mutation and exposure to infection, which means it may be preventable with treatments to stimulate or ‘prime’ the immune system in infancy. 

 

“…it has always struck me that something big was missing, a gap in our knowledge – why or how otherwise healthy children develop leukaemia and whether this cancer is preventable.”

 

The landmark paper is published in Nature Reviews Cancer. 

The first step involves a genetic mutation that occurs before birth in the foetus and predisposes children to leukaemia — but only 1% of children born with this genetic change go on to develop the disease. 

The second step is also crucial. The disease is triggered later, in childhood, by exposure to one or more common infections, according to Greaves. But primarily in children who experienced ‘clean’ childhoods in the first year of life, without much interaction with other infants or older children. 

 

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Acute lymphoblastic leukaemia is particularly prevalent in advanced, affluent societies and is increasing in incidence at around 1% per year. 

Greaves suggests childhood ALL is a paradox of progress in modern societies — with a lack of microbial exposure early in life resulting in immune system malfunction. 

 

Challenging Previous Research

Greaves research challenges previous reports of possible environmental causes, such as ionising radiation, electricity cables, electromagnetic waves or man-made chemicals — arguing that none are supported by robust evidence. 

Instead, he presents strong evidence for a ‘delayed infection’ theory for the cause of ALL, in which early infection in beneficial to prime the immune system, but later infection in the absence of earlier priming can trigger the disease. 

 

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He suggests that childhood leukaemia, in common with type 1 diabetes, and other autoimmune diseases and allergies might be preventable if a child’s immune system is properly ‘primed’ in the first years of life — potentially sparing children the trauma and life-long consequences of chemotherapy. 

Evidence that helped build the case included:

  • An outbreak of swine flu in Milan that led to seven children getting leukaemia.
  • Studies showing children who went to nursery or had older siblings, which expose them to bacteria, had lower rates of leukaemia.
  • Breastfeeding – which promotes good bacteria in the gut – protects against leukaemia.
  • Lower rates in children born vaginally than by caesarean section, which transfers fewer microbes.
  • Animals bred completely free of microbes developed leukaemia when exposed to an infection.

“The research strongly suggests that acute lymphoblastic leukaemia has a clear biological cause and is triggered by a variety of infections in predisposed children whose immune systems have not been properly primed,” Professor Greaves said. 

 

Understanding Childhood Leukaemia

 

The Disease Could Be Preventable

Population studies have found that early exposure to infection in infancy such as daycare attendance and breastfeeding can protect against ALL, most probably by priming the immune system. This suggests that childhood ALL may be preventable.

Professor Greaves is now investigating whether earlier exposure to harmless ‘bugs’ could prevent leukaemia in mice – with the possibility that it could be prevented in children through measures to expose them to common but benign microbes.

Greaves emphasises two caveats. Firstly, while patterns of exposure to common infections appear to be critical, the risk of childhood leukaemia, like that of most common cancers, is also influenced by inherited genetic susceptibility and chance.

Secondly, infection as a cause applies to ALL specifically – other rarer types including infant leukaemia and acute myeloid leukaemia probably have different causal mechanisms.

“I have spent more than 40 years researching childhood leukaemia, and over that time there has been huge progress in our understanding of its biology and its treatment – so that today around 90% of cases are cured,” Greaves said. 

“But it has always struck me that something big was missing, a gap in our knowledge – why or how otherwise healthy children develop leukaemia and whether this cancer is preventable.”

“This body of research is a culmination of decades of work, and at last provides a credible explanation for how the major type of childhood leukaemia develops.”