Professor Mel Greaves, Institute of Cancer Research

31 July 2009

Collateral DNA damage as an indicator of prior aetiological exposures in infant leukaemia.

Amount of grant: £82,421

Completion date: July 2009

Infant leukaemia (ie. leukaemia in children under one year of age) is a unique and particularly malignant variety of the disease.

Professor Greaves and team discovered some years ago that the major mutation that drives this leukaemia (a fusion gene called MLL-AF4) arises before birth.

This includes evidence from identical twins in which there is a 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.

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.

The team elected to test this by screening for DNA or chromosomal damage in the blood cells of mothers whose offspring had developed leukaemia (compared with mothers of healthy infants).

Three different assays were successfully developed for DNA/chromosomal damage detection. One of these proved unsuitable for the maternal blood samples provided (from Brazil), one gave a negative or uninformative result. The third assay, specific mutation detection, looks more promising as a sensitive read-out and this will now be pursued in follow-on studies.