Friday 29 October 1999
STRICT EMBARGO: 00.01am Friday 29th October 1999: Most cases of childhood leukaemia start in the womb. This is the finding of a paper from scientists at the Institute of Cancer Research, funded by the Leukaemia Research Fund, reported in today's The Lancet*.
In a key study investigating the causes of acute lymphoblastic leukaemia (ALL) in 2-5 year-olds, research led by Professor Mel Greaves from the LRF Centre for Cell and Molecular Biology at the Institute found that a vital gene defect implicated in the children's cancer could be traced back to before their birth, yet had not been inherited.
The work underscores the researchers' findings of two years ago that made a similar connection in a much rarer form of leukaemia found in babies.
Acute lymphoblastic leukaemia (ALL) is diagnosed in around 400 children in the UK every year. It accounts for about 80% of leukaemia cases in children and has a distinct peak in incidence in 2-5 year-olds.
"However, although vitally important in the development of leukaemia, this first genetic mishap in the womb is not the only change required for full blown leukaemia to occur," said Professor Greaves.
His team's earlier work on leukaemia in twins indicates that a post natal event to promote full blown leukaemia is also required.
This new discovery provides an essential time frame for identifying key exposures.
The work, in collaboration with researchers at the Royal Manchester Children's Hospital and in Monza, Italy is an elegantly simple idea but has required the development of highly sensitive probes which can identify very small numbers of leukaemia cells in newborn blood samples known as Guthrie cards (or blood spots), which are routinely taken soon after birth by heel prick.
Leukaemia cells taken from children with ALL had an altered or mutated gene called TEL-AML1, one of the most common molecular abnormalities in children with leukaemia. Using their specific molecular probes, the researchers were able to backtrack the appearance of this mutation and detect its presence in the neonatal blood spots of the patients.
Their striking result provides direct evidence that the common form of leukaemia in children originates via a gene defect that arises before birth, during the development of the blood cells in the foetus.
Professor Greaves said: "We conclude that the common form of childhood leukaemia frequently originates pre-natally and probably does so in most cases. Since studies of identical twins suggests a prenatal origin in children diagnosed up to 14 years it is possible that paediatric leukaemia in general is almost invariably initiated before birth.
"We still do not know what leads to the initial gene abnormality in the womb and the essential post-natal mutation," he said, adding that, "an abnormal response to infection is a strong candidate for inducing the critical second hit".
LRF Scientific Director, Dr David Grant, said that the UK researchers are leading the international field to resolve this important medical problem that could eventually lead to preventive measures.
Dr Peter Rigby, Chief Executive of the Institute of Cancer Research commented:
"This research marks an important step in the fight against leukaemia. We are making real progress and this new knowledge takes us further towards a complete understanding of a disease which affects around 1 child in 2,000 in the UK."
In particular the UKCCCR Childhood Cancer Study, now coming to completion, ought to help in resolving the problem. The Study is the most systematic ever of the possible exposures, including infection and others such as radiation, that may cause mutations leading to leukaemia and other cancers in children.
Professor Greaves commented: "The puzzle of childhood leukaemia is unfolding. There is now a real prospect that it will be solved over the next few years."
* The Lancet: Pre-natal origin of acute lymphoblastic leukaemia in children. 30th October 1999
For further information please contact:
Andrew Trehearne, Leukaemia Research Fund
0207 269 9068
0208 520 0653 (home)
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