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Leukaemia cell culprit discovered

Isabella (l) and Olivia both have the pre-leukaemic stem cells

The twins' story

A study of four-year-old twin girls has identified a rogue cell that is the root cause of childhood leukaemia.

The finding could mean more specific and less intensive treatments for all children with the blood cancer.

Both twins were found to have the "pre-leukaemic" cells in their bone marrow, although to date only one has developed leukaemia.

UK researchers reported in Science that a second genetic mutation is needed for full-blown disease to develop.

Leukaemia occurs when large numbers of white blood cells take over the bone marrow leaving the body unable to produce enough normal blood cells.

Now we know about the cell, hopefully we can find an Achilles heel we can target
Professor Tariq Enver
Along with lymphoma it accounts for almost half of childhood cancers.

Olivia Murphy, from Bromley in Kent, developed acute lymphoblastic leukaemia when she was two-years old - but so far her twin sister, Isabella, is healthy.

Researchers found they both have "pre-leukaemic stem cells" containing a mutated gene, which forms when the DNA is broken and rejoined at another point.

The pre-leukaemic cells are transferred from one twin to the other in the womb through their shared blood supply.

But it takes another genetic mutation in early childhood for the cells to cause disease.

This second mutation, which may be caused by infection, occurred in Olivia but not Isabella.

Doctors do regular tests on Isabella to look for signs of the cancer but once she reaches adolescence it is thought the rogue cells will disappear.

Achilles heel

About 1% of the population is thought to be born with pre-leukaemia cells. Of these, 1% receive the second "hit" that leads to cancer.

Current treatments are far too aggressive to justify eliminating the rogue cells before cancer develops, which also means screening is unlikely.

But attacking the pre-leukaemic cells in children with leukaemia would be a better way of treating the disease and ensuring it does not come back, the researchers said.

Study leader Professor Tariq Enver, from the Medical Research Council Molecular Haematology Unit in Oxford, said: "These are the cells which drive and maintain the disease.

"Now we know about the cell, hopefully we can find an Achilles heel we can target."

Professor Mel Greaves, from the Institute of Cancer Research and co-author on the study, said he suspected that the stem cells could escape conventional chemotherapy and cause relapse.

He said the study in the twins had been unique.

"There is an element of chance, we still have to work out why it happens in one child and not the other.

"We're pretty certain it's triggered by common childhood infection."

Dr Phil Ancliff, consultant in paediatric haematology at Great Ormond Street Hospital, said 90% of children now survived leukaemia because of intensive chemotherapy, but that it came at a price.

Olivia lost the sight in one eye after she was unable to fight an infection due to her cancer treatment.

"A significant number of children are now being over-treated but we don't know which children," he said.

In the future, he added, children could be tested to see if the stem cells had been killed off after the first few weeks of chemotherapy with some being able to stop treatment earlier, sparing them harmful side-effects.

Dr Bruce Morland, consultant paediatric oncologist at Birmingham Children's Hospital and chairman of the Children's Cancer and Leukaemia Group, said: "The identification of the leukaemic stem cell has been one of the 'Holy Grails' for cancer biologists and this study certainly brings us one step closer."

Professor Vaskar Saha, professor of paediatric oncology at Cancer Research UK, said: "This important paper shows how leukaemia develops, and how it can persist even after therapy.

"By identifying the cells involved, it raises the hope that we will be able to identify children at risk of relapse, and develop new, targeted drugs to treat the disease."

Source - © BBC MMVIII

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