Common infections may trigger leukaemia
UK scientists have identified a molecule that provides the first experimental evidence as to how leukaemia may be triggered by common childhood infections.
A team at the Institute of Cancer Research (ICR) found that a naturally-occurring molecule called TGF-beta, which is produced in response to infection, caused pre-leukaemic stem cells to multiply rapidly at the expense of normal cells.
The discovery supports the theory that common infections may trigger the onset of childhood leukaemia in individuals with a genetic predisposition to the disease.
Dr Anthony Ford from ICR revealed: "We had already identified that a genetic mutation occurring in the womb created these pre-leukaemic cells.
"But we have been looking for a trigger that could send these cells down the pathway to leukaemia. We believe TGF-beta is part of that missing link."
The genetic mutation that creates these pre-leukaemic cells involves the accidental joining-together of two genes - TEL (ETV6) and AML1 (RUNX1).
This was discovered in a study of identical twin girls, which revealed that pre-leukaemic cells grow in the bone marrow of individuals with this faulty gene for up to 15 years.
However, not everyone with the faulty gene will experience leukaemia. As many as one in 100 newborns are thought to carry the gene, yet only one in 100 of these children go on to develop leukaemia, indicating that other factors are required for the disease to develop.
The latest study, which appears in the Journal of Clinical Investigation, shows that the molecule TGF-beta can create the conditions required for pre-leukaemic cells to multiply, increasing the chance that some will become further damaged and trigger the onset of full leukaemia.
Dr Shabih Syed, scientific director at Leukaemia Research, which part-funded the study, commented: "Before this study, there had been only circumstantial evidence to implicate infections in the progression from a child carrying pre-leukaemic cells to actually having leukaemia. There was no evidence of the mechanism by which this might happen.
"While infection is clearly only one factor in triggering progression, this study greatly increases the strength of evidence for its role in the commonest form of childhood leukaemia."
Vaskar Saha, Cancer Research UK's professor of paediatric oncology, added: "Some studies have found evidence for a link between infection and childhood leukaemia, but exactly how infection affects a child's risk of developing the disease is still unclear.
"This is the first step in understanding why this link might exist. While this is exciting, this is one step in a series of genetic events that could lead to the disease.
"We need to have conclusive evidence on the risk factors for childhood leukaemia and an understanding of a mechanism behind its link with infection before we can make recommendations on how to avoid this disease."