Twins help scientists identify cancer stem cells

A pair of twins has helped an international team of scientists identify the cancer stem cells which cause the most common form of childhood leukaemia, acute lymphoblastic leukaemia (ALL), the
findings could lead to the development of better drugs with fewer side effects.

The work, which was partly funded by the EU, is published in the latest edition of the journal Science.

At the heart of the study is a pair of identical twin children called Olivia and Isabella, who come from Bromley in the UK. In 2005, when the girls were just two years old, Olivia was diagnosed
with ALL and started on treatment. Her twin has so far remained disease free. The scientists hoped that by comparing the twins’ genes they would be able to identify the mutations that had
caused Olivia to develop the disease.

Analyses of the girls’ blood revealed that both had genetically abnormal cells in their blood. These ‘pre-leukaemic’ stem cells reside in the bone marrow and either remain dormant or develop
into full-blown leukaemia stem cells.

The pre-cancerous cells arise from an abnormal fusion of two genes during pregnancy. The resulting gene produces a hybrid protein called TEL-AML1 which gives the cell the ability to survive and
renew itself. If additional mutations take place during childhood, they can trigger the onset of the disease.

‘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,’ said Professor Mel
Greaves of the Institute of Cancer Research. ‘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.’

Current treatments for ALL are extremely aggressive and can have severe side effects; Olivia is now blind in one eye following an infection that her body was unable to fight while she was on
chemotherapy. The scientists hope their findings will lead to the development of less aggressive, more effective treatments for the disease.

‘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 Medical Research Council. ‘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.’

ALL is a form of cancer which affects the white blood cells and the cells responsible for producing them in the bone marrow. It can affect children of any age but is most common between the
ages of one and four. The survival rate is currently 75 to 80%.

EU support for the work came from the EuroCSC (‘Targeting cancer stem cells for therapy’) project, which is funded under the ‘Life sciences, genomics and biotechnology for health’ thematic area
of the Sixth Framework Programme (FP6).

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