Thursday 16 January 2008
A breakthrough study of identical twins has for the first time confirmed the existence of cancer stem cells that cause the most common form of childhood cancer, acute lymphoblastic leukaemia (ALL) – backing evidence that this childhood cancer starts in the womb. The research should lead to less aggressive treatment for childhood ALL and provides the hope of new, more effective drugs.
Scientists from The Institute of Cancer Research together with colleagues at The University of Oxford and Great Ormond Street Hospital, funded by Leukaemia Research and the Medical Research Council (MRC), have compared cells in the blood of three-year-old identical twins Olivia, who is being treated for leukaemia, and Isabella who is healthy. They found that both twins had the same genetically abnormal primitive cells in their blood. These 'pre-leukaemic' stem cells reside in the bone marrow and either 'lay dormant' or go on to develop into full-blown leukaemia stem cells.
The new research, published in the journal Science, shows that pre-cancerous stem cells arise from an abnormal fusion of two genes during the mother's pregnancy to create a hybrid protein 'TEL-AML1'. This genetic mistake can set in motion a series of events that cause the cells to become leukaemic. The authors confirmed their findings in the twins, Olivia and Isabella, by putting the TEL-AML1 gene into human cord blood cells, which were then transplanted into mice that had no immune system. They found that the pre-leukaemic stem cells found in both twins also became established in the bone marrow of the mice, which proved the 'self renewing' nature of the cells and confirmed a direct link between the specific genetic malfunction and leukaemia.
Professor Tariq Enver, who led the research at the MRC Molecular Haematology Unit, says: "This research means that we can now test whether the treatment of acute lymphoblastic leukaemia in children can be correlated with either the disappearance or persistence of the leukaemia stem cell. Our next goal is to target both the pre-leukaemic stem cell and the cancer stem cell itself with new or existing drugs to cure leukaemia while avoiding the debilitating and often harmful side effects of current treatments."
The seriousness of these side effects is all too clear for Olivia herself – she became blind in one eye as a result of an infection that her body was unable to fight due to the chemotherapy treatment.
Professor Mel Greaves, of The Institute of Cancer Research and co-author of the paper added: "This study of a twin pair discordant for leukaemia has identified the critical stem cells that initiate the disease and maintain it in a covert state for several years. We suspect that these cells can escape conventional chemotherapy and cause relapse during or after treatment. These are the cells that dictate disease course and provide the bull's eye to target with new therapies."
The findings are published on 18 January 2008 in the journal Science.
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The family of the twins and the authors of the report are available for interview.
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Notes to Editors
- The report will be published on 18 January 2008 in the journal Science under the title 'Initiating and tumor-propagating cells in TEL-AML1- associated leukemia'. Senior authors: Professor Tariq Enver of the Weatherall Institute for Molecular Medicine, University of Oxford, Professor Mel Greaves of the Institute of Cancer Research, Sutton and Dr Phil Ancliff, Great Ormond Street Hospital.
- The work was funded by a Specialist Programme Grants to Professors Enver and Greaves from Leukaemia Research, with additional funding from the Medical Research Council and EuroCSC.
- Leukaemia Research is the only national charity devoted exclusively to improving treatments, finding cures and learning how to prevent leukaemia, Hodgkin's lymphoma and other lymphomas, myeloma and the related blood disorders, diagnosed in 24,500 people in the UK every year.
- Over the next five years, Leukaemia Research urgently needs to raise over £100million to commit to new research. From basic laboratory research to clinical trials with patients, Leukaemia Research is committed to saving lives by funding high quality, carefully selected research throughout the UK. Further information, including patient information booklets, is available from www.lrf.org.uk or on 020 7405 0101.
- The Medical Research Council is dedicated to improving human health through excellent science. It invests on behalf of the UK taxpayer. Its work ranges from molecular level science to public health research, carried out in universities, hospitals and a network of its own units and institutes. The MRC liaises with the Health Departments, the National Health Service and industry to take account of the public’s needs. The results have led to some of the most significant discoveries in medical science and benefited the health and wealth of millions of people in the UK and around the world. www.mrc.ac.uk