30 May 2018

A recent review has highlighted a potential link between excessive hygiene and acute lymphoblastic leukaemia (ALL).

Professor Mel Greaves from The Institute of Cancer Research, London, says he believes childhood ALL develops because of a two-step process of genetic mutation and exposure to infection.

Treatments to stimulate the immune system in infancy could help to prevent the disease, according to Professor Greaves.

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

He says the disease is likely triggered in childhood following exposure to one or more common infections - but it is primarily among children who experienced 'clean' childhoods in the first year of life, without much interaction with other infants or older children.

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

He also says his research “busts some persistent myths about the causes of leukaemia, such as the damaging but unsubstantiated claims that the disease is commonly caused by exposure to electro-magnetic waves or pollution.”

Writing in Nature Reviews Cancer, he describes compiling more than 30 years of research into the genetics, cell biology, immunology, epidemiology and animal modelling of childhood leukaemia.

He said there is evidence that ALL is caused by “delayed infection”, in which early infection is beneficial to prime the immune system. However, later infection in the absence of earlier priming can trigger leukaemia, he claimed.

Professor Greaves suggests that childhood leukaemia, in common with type I diabetes, other autoimmune diseases and allergies, might be preventable if a child's immune system is properly ‘primed’ in the first year of life.

His studies of identical twins with ALL showed that two mutations were required: the first arises in one twin in the womb but produces a population of pre-malignant cells that spread to the other twin via their shared blood supply. The second mutation arises after birth and is different in the two twins.

Human poopulation studies, as well as animal modelling, suggest the second genetic ‘hit’ can be triggered by infection - in one unique cluster of cases investigated by Professor Greaves and colleagues in Milan, they found all cases were the result of infection with influenza virus.

Researchers also engineered mice with an active leukaemia-initiating gene, and found that when they moved them from an ultra-clean, germ-free environment to one that had common microbes, the mice developed ALL.

Other population studies have found that early exposure to infection, such as day care and breastfeeding, can protect against ALL, which could suggest that childhood ALL may be preventable.

Professor Greaves is now investigating if earlier exposure to harmless ‘bugs’ could prevent leukaemia in mice.

 “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,” he 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.”

Professor Paul Workman, chief executive of The Institute of Cancer Research, London, added: “It’s exciting to think that, in future, childhood leukaemia could become a preventable disease as a result of this work. Preventing childhood leukaemia would have a huge impact on the lives of children and their families in the UK and across the globe.”

Source: Greaves, M., 2018. A causal mechanism for childhood acute lymphoblastic leukaemia. Nature Reviews Cancer, p.1.

Link: https://www.nature.com/articles/s41568-018-0015-6


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