Monday 12 October 2009
A rare case of a mother and her infant developing the exact same cancer has allowed an international team of researchers to solve a puzzle that has perplexed scientists and clinicians for a century.
Scientists at The Institute of Cancer Research (ICR) and colleagues in Japan, with funding from Leukaemia & Lymphoma Research, investigated a situation in which leukaemic cells appeared to have defied accepted theories of biology and spread through the womb from a Japanese woman to her daughter.
Around 30 previously known cases of a mother and infant appearing to share the same cancer, usually leukaemia or melanoma, had already raised suspicions that such spread was possible. But there was no genetic evidence to support this theory, and scientists did not know how it could happen as the baby’s immune system should have recognised and destroyed any invasive cancer cells that were of maternal – and therefore ‘foreign’ – origin.
In a study published in Proceedings of the National Academy of Sciences today, the ICR scientists used advanced genetic fingerprinting to prove for the first time that the infant’s leukaemic cells were unquestionably of maternal origin.
They found both patients’ leukaemic cells carried the identical mutated cancer gene (called BCR-ABL1), but the infant had not inherited this gene. This meant the child could not have developed this type of leukaemia in isolation.
To investigate how the cells could have crossed the placental barrier and survived in the offspring, the scientists looked for evidence of some form of immunological acceptance or tolerance of the foreign cells by the foetus.
They examined the genes of the cancer cells in the infant and found a deletion mutation – some DNA missing in the region that controls expression of the major histocompatibility locus (HLA). This was significant because HLA molecules primarily distinguish one individual, and his or her cells, from another, so the absence of these molecules on the cancer cells meant the infant’s immune system would not have recognised that they were foreign.
Professor Mel Greaves, who led the study at the ICR, says: “It appears that in this and, we presume, other cases of mother to offspring cancer, the maternal cancer cells did cross the placenta into the developing foetus and succeeded in implanting because they were invisible to the immune system.
“We are pleased to have resolved this longstanding puzzle. But we stress that such mother to offspring transfer of cancer is exceedingly rare and the chances of any pregnant woman with cancer passing it on to her child are remote.”
Dr David Grant, Scientific Director at Leukaemia Research, said: “The important message from this fascinating piece of research is that leukaemia cells can be destroyed by the immune system. Harnessing the power of the immune system to first cure and then protect patients from leukaemia is one of our priority areas of research.”
The study was funded by Leukaemia & Lymphoma Research, the Kay Kendall Leukaemia Fund and the ICR.
For further information, please contact Henry Winter at Leukaemia & Lymphoma Research Press Office on 020 7269 9019, 07824 375880 or email: [email protected]
Notes to Editors:
The study will be published on online on 12 October in the journal Proceedings of the National Academy of Sciences under the title: ‘Immunologically silent cancer clone transmission from mother to offspring’. Corresponding author: Professor Mel Greaves, Section of Haemato-Oncology, The Institute of Cancer Research, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom.
Leukaemia & Lymphoma Research
Leukaemia Research is the only national charity devoted exclusively to improving treatments, finding cures and learning how to prevent leukaemia, Hodgkin’s and other lymphomas, myeloma and the other related blood disorders, diagnosed in 24,500 people in the UK every year. Further information, including patient information booklets, is available from www.llresearch.org.uk or call 020 7405 0101.
The Institute of Cancer Research
The Institute of Cancer Research is Europe’s leading cancer research centre with expert scientists working on cutting-edge research. In 2009, the ICR marks its 100 years of groundbreaking research into cancer prevention, diagnosis and treatment. In December 2008, the ICR was ranked as the UK’s leading academic research centre by the Times Higher Education’s Table of Excellence, based on the results of the Higher Education Funding Council’s Research Assessment Exercise. It is home to the world’s leading academic paediatric childhood cancer drug development unit. In the next 10 years our scientists aim to develop effective drugs to treat the four cancers responsible for the majority of childhood cancer deaths. To achieve this and our other research, The ICR – as a charity – relies on voluntary income, for more information visit www.icr.ac.uk.