Childhood leukemia probably driven by common infections such as the flu

Childhood leukemia is driven by common childhood infections that encounter pre-cancerous cells in the blood, researchers believe.

Experts at the Institute of Cancer Research (ICR) in London have found that babies develop the risk of leukemia in the womb, but will not go on to develop the disease without another “hit” from a viral or bacterial infection, such as influenza.

The research highlights the importance of allowing infants to socialize with other children early in life, in order to strengthen the immune system against infections.

The discovery came from studying twin pairs, where only one initially developed acute lymphoblastic leukemia (ALL) – the most common type of cancer in children.

Identical twins are about 15-25 percent more likely to develop ALL if their sibling already has the disease, while less than one percent of non-identical twins or other siblings go on to develop the disease.

Researchers followed the twins for up to 15 years and found that the high risk only applies if the identical twins shared a single placenta before birth – which only happens in about 60 percent of identical twin pairs.

Findings “confirm that disease can be traced back to the womb”

It confirms that the conditions needed to trigger leukemia first occur in the womb, and even the healthy twin will carry “pre-leukemia” cells in the blood, which have arisen through a spontaneous developmental error, and passed between the two.

But clinically silent cells will not develop into cancer without a “hit” after birth, probably from common childhood infections.

Prof Sir Mel Greaves, founder of the Center for Evolution and Cancer and professor of cell biology at the Institute of Cancer Research, London, said: “Our study provides new insights into the origins of childhood acute lymphoblastic leukaemia.

“These new findings confirm that the disease can be traced back to the womb when pre-leukemia cells are spread via the twins’ shared blood supply.

“What remained a mystery until now was why sometimes only one twin is diagnosed with leukemia.

“We still don’t know for sure what causes the first ‘hit’ of genetic changes in the womb, but we think the second ‘hit’ of genetic changes is likely triggered by common childhood infections – opening up the possibility of ‘priming’ the immune system in infancy to avoid the development of the disease later in life.”

Acute lymphoblastic leukemia is the most common type of childhood cancer, and accounts for 80 percent of leukemia cases in children.

The team is now focused on finding the second infection-driven hit after birth.

Strengthening the gut can protect children from disease

They believe that the gut microbiome may play a key role in protecting children from developing leukemia even if they have pre-cancerous cells. Although vaccines have little effect on preventing ALT, boosting the gut early in life can help.

Prof Greaves added: “The risk of ALL is increased by caesarean section, lack of breastfeeding and lack of social contact in infancy.

“Conversely, playgroup attendance in infancy is protective. So to some extent risk can be modified without medical intervention.”

The findings will also allow doctors to assess the risk of ALL for twins, first by determining whether the twins are identical and share a placenta, and then by regularly tracking the levels of pre-leukemia cells in the blood.

Sarah McDonald, deputy head of research at Blood Cancer UK, which funded the work, said: “Understanding the mechanism of how cancer develops in identical twins and why often only one develops leukemia is an important question to answer.

“It helps us understand both the risk of the other sibling developing leukemia and provides insight into how leukemia develops in all children.

“This research shows that in cases where one twin develops leukemia, and both twins share a placenta during pregnancy, two events are needed to determine whether the other sibling develops the disease – one before birth and the other after.”

The research was published today in the journal Leukaemia.

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