The twins who unlocked the secrets of leukaemia

British girls are behind dramatic breakthrough in medicine

A study of these identical twin girls has led to a new understanding of the causes of childhood leukaemia and could revolutionise the treatment – and possibly prevention – of the potentially lethal disease. The detailed investigation of the two British girls has, for the first time, enabled medical researchers to track down the source of the cancerous stem cells in the blood that can lead to leukaemia in the first few years of life.

Olivia and Isabella Murphy, aged four, from Bromley in Kent, have provided science with an astonishing insight into the nature of leukaemia because of the highly unusual situation where both of them are at risk of the disease but only Olivia developed it.

Scientists believe the findings will enable them to develop better treatments with fewer and less serious side effects. It could also help in the search for the ultimate cause of the condition, which is newly diagnosed in 500 children each year in Britain.

Olivia and Isabella share the same genetic mutation to the blood-forming cells of the bone marrow, which must have occurred during their time in the womb because neither of their parents was found to have the same mutation.

However, only Olivia went on to develop leukaemia because she was unfortunate enough to have suffered a second mutation after birth, which triggered the onset of the cancer.

Scientists believe the mutation in the womb – which occurred in one of the foetuses but was passed to the other via circulating blood cells – caused both girls to be born with pre-cancerous stem cells in their blood, which predisposed them to leukaemia.

However, Olivia suffered the critical second mutation after the twins were born. That led to the development of the full-blown blood cancer which had to be treated with chemotherapy drugs that stunted her growth and led to a serious eye infection.

It was that difference between the two girls that enabled the scientists to locate the pre-cancerous stem cells in both children and then to figure out the sequence of genetic mutations.

Isolating the pre-cancerous stem cells from Olivia and Isabella, who will be five next month, could prove pivotal in the further understanding and treatment of childhood leukaemia, said Professor Mel Greaves of the Institute of Cancer Research in Sutton, Surrey.

"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," he said.

Olivia has successfully undergone treatment for leukaemia and is in remission. However, she is blind in one eye caused by an infection after her time on chemotherapy, which affected her immune system.

Her mother, Sarah, 35, said Olivia's treatment had affected her growth and her hair had become curly, but it had at least cleared many of the pre-cancerous blood cells identified by the research team.

She said she was worried about Isabella."Olivia is almost clear but ... Isabella still has a long way to go. They said the cells might die off naturally but obviously it is something which is hanging over us," Mrs Murphy said.

"It is quite hard but we have always tried to remain positive, although that is easy to say. It would be very hard to have to get through it twice but we are trying not to think about it too much."

Professor Greaves, whose study with Professor Tariq Enver of the Medical Research Council's Weatherall Institute for Molecular Medicine at Oxford University is published in the journal Science, said the genetic mutation found in the pre-cancerous stem cells of the twins was caused by the merging of two genes known as TEL and AML-1.

When the scientists inserted the hybrid TEL-AML-1 gene into human umbilical cord cells and inserted those mutated cells into mice, the mutated cells became self-renewing with the animals' bone marrow, just like they are in children such as Olivia and Isabella.

"This research means 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 cells," said Professor Enver of Oxford University. "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."

Bruce Morland, a childhood cancer specialist at Birmingham Children's Hospital, said the study brought scientists one step closer to the "holy grail" of identifying leukaemic stem cells.

"By determining the characteristics of the leukaemic stem cells it is ultimately the hope of clinicians that therapies can be specifically targeted to the leukaemia, thus sparing the patient from some of the significant side effects of conventional chemotherapy treatment," he said.

Most common childhood cancer

500 new cases of childhood leukaemia in UK per year

1 in 3 of all cancer cases among children is leukaemia

50 percentage of all cases affecting under-five age group

80% survival rate of commonest form (acute lymphoblastic leukaemia)

55% cure rate for acute myeloid leukaemia (which accounts for 1 in 4 cases)

1 in 10 survival rate in the 1960s

0 survival rate pre-1960s

1.4% rise in in childhood lymphoid leukaemia cases in Europe from 1970 to 1999

45.6 per million number of cases among black children in the US during the 1980s and 1990s

27.8 per million number of cases among white children in the same period

50 per million number of cases among Hispanics living in California

Source: leukaemia.org

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