A breakthrough study of identical twins has for the first time confirmed the existence of pre-leukemic stem cells that cause the most common form of childhood cancer, acute lymphoblastic leukemia (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 3-year-old identical twins Olivia, who is being treated for leukemia, and Isabella who is healthy. They found that both twins had the same genetically abnormal primitive cells in their blood. These 'pre-leukemic' stem cells reside in the bone marrow and either 'lay dormant' or go on to develop into full-blown leukemia stem cells.
The new research 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 leukemic. The researchers 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-leukemic 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 leukemia.
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 leukemia in children can be correlated with either the disappearance or persistence of the leukemia stem cell. Our next goal is to target both the pre-leukemic stem cell and the cancer stem cell itself with new or existing drugs to cure leukemia 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 added: "This study of a twin pair discordant for leukemia 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."
Illustration: Olivia and Isabella, The Guardian.
Leukaemia Research News Release (01/16/08)
The Guardian (01/17/08)
Good News Blog (01/17/08)
ABC News/Australia (01/18/08)
Sky News (01/18/08)
The Earth Times (01/18/08)
Medical News Today (01/18/08)
Abstract (Science 18 January 2008: Vol. 319, No. 5861, pp. 336 – 339)