ICR Study Suggests Timing of Childhood Infection Exposure May Influence Development of Acute Lymphoblastic Leukaemia

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(IN BRIEF) Researchers at The Institute of Cancer Research have published new findings showing that delayed exposure to common microbes may trigger childhood acute lymphoblastic leukaemia (ALL) in genetically susceptible individuals, while early-life microbial exposure may help protect against the disease. Using genetically engineered mice, scientists demonstrated that timing of microbial exposure plays a critical role in immune system development and cancer risk. The study provides strong experimental support for the delayed infection theory of childhood leukaemia first proposed by Professor Sir Mel Greaves and raises the possibility that future prevention strategies could involve microbiome-supporting interventions during infancy.

(PRESS RELEASE) LONDON, 15-May-2026 — /EuropaWire/ — Researchers at The Institute of Cancer Research have produced new experimental evidence supporting a long-standing theory explaining how the timing of exposure to common infections may influence the development of childhood acute lymphoblastic leukaemia (ALL), the most common cancer affecting children.

The study, published in the journal Haematologica, strengthens the delayed infection hypothesis first proposed decades ago by Professor Sir Mel Greaves, suggesting that a lack of microbial exposure early in life may leave the developing immune system vulnerable to abnormal responses later in childhood that can contribute to leukaemia development in genetically susceptible individuals.

Using genetically engineered mice carrying the ETV6::RUNX1 fusion — one of the most common initiating genetic alterations linked to childhood ALL — researchers demonstrated that delayed exposure to common but otherwise harmless microbes could trigger the disease. In contrast, early and continuous exposure to a diverse microbial environment appeared to protect against leukaemia development.

The findings provide some of the clearest experimental support to date for the idea that childhood ALL develops through a two-step process. The first stage occurs before birth, when genetic mutations or chromosomal abnormalities arise in developing foetal blood cells. However, these early alterations alone are usually insufficient to cause cancer, and many children carrying such mutations never develop leukaemia.

According to the theory, a second genetic “hit” is required after birth. This often involves additional mutations in developing immune cells, particularly affecting genes involved in normal B-cell maturation. Researchers believe these secondary mutations may be triggered by abnormal immune responses to infections encountered later in childhood if the immune system has not been properly “trained” through early microbial exposure.

Previous epidemiological studies had already pointed toward this possibility. Children born via Caesarean section, primarily formula-fed infants and those with limited social interaction during their first year of life have been observed to face a slightly increased risk of ALL. Scientists have suggested that reduced microbial exposure during infancy may impair normal immune system calibration.

To directly test the hypothesis, the ICR team used a unique experimental setup involving two separate mouse facilities that differed in microbial diversity despite both being classified as specific pathogen free environments. One facility maintained an ultra-clean environment with minimal microbial presence, while the other contained a broader range of non-harmful microbes including bacteria, viruses and unicellular organisms.

Researchers transferred genetically susceptible mice from the ultra-clean environment into the more microbially diverse setting shortly after weaning. Nearly one quarter of these mice later developed ALL. By comparison, mice born and raised continuously within either environment did not develop the disease, nor did mice introduced after the microbial environment had been eliminated during pandemic-era fumigation procedures.

Analysis of the mice also revealed that those raised in the more diverse microbial environment developed richer gut microbiomes containing bacterial populations associated with healthy immune development.

The researchers believe the findings highlight the existence of a critical developmental window during infancy in which exposure to a range of microbes may help regulate and educate the immune system. Missing this period could increase the likelihood of exaggerated inflammatory responses later in life, potentially increasing cancer risk among children already carrying pre-leukaemic genetic changes.

While the researchers stressed that the findings do not support deliberate exposure of children to harmful infections, they suggest future preventative strategies could involve safer approaches such as microbiome-supporting diets, probiotics or other interventions designed to encourage healthy immune development during infancy.

Professor Greaves said the findings strongly support the delayed infection model for childhood ALL and raise the possibility that the disease could one day become preventable through carefully designed microbiome enrichment strategies during early life.

Joint first author Elham Shamsaei said the study does not alter current treatments or medical advice for families affected by ALL, but it may open the door to future prevention strategies focused on restoring healthier interactions between the developing immune system and the microbial environment.

The research received funding support from Cancer Research UK, Children’s Cancer and Leukaemia Group, the Artemis Fund and the Edwards Family Prevent ALL Fund.

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SOURCE: The Institute of Cancer Research