Stem cells which cause childhood leukaemia found
17 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 funded by the UK’s leading blood cancer charity 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.
Olivia and Isabella
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.”
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Notes to Editors
Ref MRC/05/2008
