Professor Mel Greaves, Institute of Cancer Research, London

Infant leukaemia (i.e. leukaemia in children under one year of age) is a biologically and clinically distinct disease.

The vast majority of infant leukaemias are caused by a change involving a break on the MLL gene on chromosome 11.

The broken gene fuses with other broken chromosomes, forming a new gene at the fusion point.

Professor Greaves and his team have provided evidence that many, if not all, infant leukaemias with MLL fusions are initiated pre-natally, in utero.

This includes evidence from monozygotic (identical) twins in which there is an extraordinarily high concordance rate of leukaemia, suggesting that all of the necessary genetic events are already acquired by the time of birth.

Similar MLL fusions are frequently found in so-called ‘secondary’ acute leukaemias (in adults or children) associated with certain types of chemotherapy drugs called topoisomerase inhibitors.

This prompted the idea that exposure to similar types of chemicals during pregnancy might initiate MLL fusions and induce any necessary secondary events to cause infant leukaemia in utero.

There is already a body of genetic and epidemiological evidence implicating the role of transplacental chemical exposure in the development of leukaemia.

Professor Greaves hypothesises that if this is indeed how infant leukaemias are caused in utero, then residual damage should be present and detectable in the DNA and chromosomes of normal cells of infant leukaemia patients and their mothers at a significantly greater frequency than in healthy children.

Continuing a long-standing collaboration with the National Institute of Cancer in Brazil, blood samples will be collected from Brazilian patients and controls, as part of ongoing genetic epidemiology studies of infant leukaemia in Brazil.

The samples will then be screened for DNA damage in normal blood T-cells.

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