Scientists believe infant leukaemia begins before birth: Study of identical twins gives clue to gene changes

SCIENTISTS are a step closer to finding the cause of infant leukaemia after studies, by a London team, of identical twins with the disease.

The researchers believe they have proved that leukaemia in children under a year old is most likely to be caused in the womb, rather than during its first year of life. They also believe this is an acquired condition, rather than inherited.

Pinpointing the onset of the disease in this way should make it easier to identify the environmental or other factor that causes the genetic changes in affected infants.

Mel Greaves, who heads the team at the Leukaemia Research Fund laboratories in the Institute of Cancer Research, said the gene that changes in infants with leukaemia is known to change in the small percentage of cancer patients that develop leukaemia after treatment with etoposide. This drug is used in lung and testicular cancers and some lymphomas. 'It could be that some substance, chemically or physically similar to etoposide is the cause of infant leukaemia,' Professor Greaves said. He hopes to include questions that will help to identify some possible candidates in the National Case Control Study, a major study of childhood cancers.

Professor Greaves said that 80 per cent of infants with leukaemia had an abnormality in exactly the same gene, known as 'HRX'. The change in the gene differs in each child, except in identical twins. Inheriting the defect could explain this.

However, if the condition had been inherited, the mutation that caused the leukaemia would have been present in all of the child's cells, and in the parents' genes. The researchers found no sign of the mutation in the parents, and in no cells in the twins other than the leukaemia cells themselves. 'An identical mutation is incredibly unlikely to occur twice in both twins,' Professor Greaves added.

The key to his team's findings is the fact that identical twins commonly share the same placenta, so blood passes between them. He believes one twin suffers the necessary change in its gene, then the leukaemia passes from one twin to the other in the womb. His team's results are published in today's issue of the science journal Nature.

The annual incidence of infant leukaemia is 1 in 100,000. Work on identical twins with the disease has been hampered by there being so few of them - about 100 recorded in clinical and scientific literature.