So Now We Know What Causes Childhood Leukaemia (ALL)

A Knighthood For Scientist: Prevention is Being Researched

Porapak Apichodilok

Scientist Professor Mel Greaves (newly knighted) is in the process of trying to create a drink that will help prevent children from developing leukemia.

After spending over 30 years researching what causes childhood leukemia, and publishing his findings, he will now focus on developing a cure.

I would have thought I would be hearing this as headline news all around the world. His name up in lights. But it was a small article in our local online paper that caught my eye.

In a day and age where anyone who spends an hour on the internet reading conspiracy theories feels they are qualified to debunk scientific research validated by decades of study, this news touched me deeply.

Prof. Greaves is based at the Institute for Cancer Research in London. The New Years honors list announced he had received a knighthood for his research of three decades investigating the causes of childhood leukemia.

His findings along with that of his colleagues from around the world were released in the journal Nature Reviews Cancer in May 2018.

According to the Medical Press, May 21, 2018, the paper presented research spanning 30 years considering the genetics, cell biology, immunology, epidemiology and animal modeling of childhood leukemia.

Professor Greaves also “challenged previous reports of possible environmental causes, such as ionizing radiation, electricity cables, electromagnetic waves or man-made chemicals — arguing that none are supported by robust evidence as major causes.”

Two of the most common types of leukemia affecting young people are acute lymphoblastic leukemia or ALL (which affects 1 in 2000 children) and acute myeloid leukemia. Treatments (which are toxic) are now effective at curing about 90% of cases, but there can be long-term side effects.

Understanding finally what causes this cancer (specifically ALL) means that scientists can finally have a chance to intervene and stop leukemia from developing in the first place. They can work on prevention.

His findings which explain why children develop leukemia are fascinating.

Having a new grandson due to be born in the next week I read a summary outlining in layman’s terms the findings of his research with great interest. As soon as I read it, I forwarded the article to my pregnant daughter.

I will try to explain it.

Childhood leukemia has been increasing at about the rate of 1% a year in the United Kingdom and Europe. Understanding this increase occurred in relatively affluent countries was vital as it is not the case in developing countries. It appears to be tracking in line with greater wealth.

What they discovered is that acute lymphoblastic leukemia “is caused by a sequence of biological events.”

1. First, there is a genetic mutation which occurs in one in twenty children.
2. The mutation is not inherited but happens as a result of an ‘accident’ in utero. This mutation (of which 1 in 20 children have had it occur) leaves the child at risk of getting leukemia later in life. Only about 1% of children who have this mutation go on to develop cancer.

What has to happen for leukemia to be triggered is what I found so fascinating.

3. A child’s immune system must be exposed to an infection in the first 12 months of the child’s life for a child with the mutation to stay healthy and not develop leukemia.

Without that confrontation with infection, in the first year of life, the immune system is not primed properly and will not work properly.

4. What that means in modern affluent societies (of which leukemia is on the rise) is that more children are NOT getting an infection in the first year of life.

The reasons for this are varied. Dirt is banished in many modern homes due to the use of antiseptic wipes, antibacterial soaps, and disinfected floors. Rates of breastfeeding have dropped, and children have fewer social contacts with others in the first year of life (giving them less contact with germs). This means there is less risk of them being exposed to infection because there is less exposure to dirt and bacteria. There are higher rates of caesareans which are more sterile and less vaginal births. Only children are less likely to be exposed to infection from older siblings bringing colds and flu into the home.

So, what happens if a child is NOT exposed to an infection in the first year of their life?

The problem is not infection. The problem is lack of infection.

5. When the baby or toddler is eventually exposed to an infection, their immune system reacts abnormally. It overreacts, and chronic inflammation can occur.

6. As inflammation increases in the body, it stimulates a chemical called cytokines to release into the blood.

7. The release of the cytokines in the blood of children who already have the mutation can result in the development of leukemia.

So, it is a two-step biological process.

First, the child who develops leukemia must have the mutation, and secondly, they must have chronic inflammation occur after NOT being exposed to enough infection to prime their immune system to work correctly in the first year of their life.

According to Medical Press, Professor 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.

Wow. Who would have thought?

We all think we are doing our best for our children by keeping our homes super clean and bugfree, but our children’s immune systems need to confront bugs to be able to start working correctly.

Professor Greaves and his colleagues do NOT want any parent to feel responsible for causing their child’s cancer. They point out that keeping a home and child free of infection is very normal behavior and there is still an element of chance in their child having to develop both genetic mutations.

So, at this stage of the research into preventing leukemia scientists are yet to find a way to STOP the occurrence of the prenatal mutual from initially occurring in the first place.

But, they are developing ways to stop the second part of the process (which is necessary for full-blown leukemia to develop) and that is finding ways to BLOCK chronic inflammation from occurring.

This is where it gets exciting.

1. Greaves and his team are concentrating on developing ways to reconstitute microbiomes that live in the gut as people in developed countries have far fewer.
2. They are also researching which gut bacteria and microbes are the most important for priming a child’s immune system.
3. They are experimenting currently with mice to see what bugs are best for stimulating their immune systems.
4. Human trials are expected to commence in the next two to three years.
5. They hope to develop a cocktail of the best microbes (maybe 6–10 species) to give to very young children in the form of a drink.
6. Scientists hope that this microbial drink would not just stop leukemia from developing in susceptible children but would also help conditions such as Type 1 Diabetes and allergies which have also both been linked to failure to expose babies to sufficient gut bacteria to prime their immune systems.

Professor Greaves hopes that developing a means of prevention will mean children are spared the trauma and life-long consequences of chemotherapy which is the current treatment.

Professor Mel Greaves comprehensive research findings A causal mechanism for childhood acute lymphoblastic leukaemia, published 21 May 2018 in Nature Reviews Cancer 18, pages 471–484 (2018) are here.