18 january 2008

Leukaemia-causing cells found

Olivia and Iabel
Identical twins Olivia and Isabella provided crucial evidence about cancer ‘stem cells’.
Scientists have discovered the cancer ‘stem cells’ that cause acute lymphoblastic leukaemia, the most common form of childhood cancer. A report of the research, which was led by Oxford University scientists, has been published in the journal Science.

The breakthrough came through studying four-year-old identical twins Olivia, who has leukaemia, and Isabella, who is healthy. They found that both twins had abnormal ‘pre-leukaemia’ stem cells in their blood that can either lie dormant in the bone marrow or develop into full-blown leukaemia stem cells. The results were then confirmed with experiments using human cord blood cells.

‘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,’ said Professor Tariq Enver of the MRC Molecular Haematology Unit at Oxford University, who led the research. ‘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 importance of avoiding such side effects is all too clear in Olivia’s case: she became blind in one eye as a result of an infection her body was unable to fight due to chemotherapy treatment.

Scientists have tracked the pre-cancerous stem cells back to an abnormal fusion of two genes that can occur during the mother’s pregnancy. This fusion creates a hybrid protein ‘TEL-AML1’; a genetic mistake that can set in motion a series of events that cause the cells to become leukaemic. The authors confirmed their findings in the twins by putting the TEL-AML1 gene into human cord blood cells, which were then transplanted into mice lacking an immune system. They discovered that the pre-leukaemic stem cells found in both twins also became established in the bone marrow of mice and confirmed a direct link between the specific genetic malfunction and leukaemia.

The research was funded by Leukaemia Research and the Medical Research Council and involved scientists from the Institute of Cancer Research and Great Ormond Street Hospital.