Culprit cell for childhood leukaemia discovered

Jan 20 2008

A study by British researchers of twin girls has identified a rogue cell that is the fundamental cause of childhood leukaemia.

The twins have been crucial to the new research, as they are genetically identical but one has developed cancer while the other has not.

The research has identified precisely the cancerous stem cells that drive the cancer and the researchers say the breakthrough could mean more effective therapies for leukaemia with fewer harmful side-effects.

Four-year-old twins Olivia and Isabella Murphy from Bromley in Kent, were both found to have the "pre-leukaemic" cells in their bone marrow, although to date only one has developed leukaemia.

Leukaemia occurs when large numbers of white blood cells take over the bone marrow and the body is then rendered unable to produce enough normal blood cells; along with lymphoma it accounts for almost half of childhood cancers.

The researchers say a second genetic mutation is needed for the full-blown disease to develop.

Olivia developed acute lymphoblastic leukaemia when she was two-years old but so far her twin sister, Isabella, remains healthy.

The researchers found both twins 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 and was discovered by comparing the twins' blood.

Isabella is subjected to regular tests by doctors for signs of the cancer but they believe once she reaches adolescence the rogue cells will disappear.

It is estimated that about 1% of the population are born with pre-leukaemia cells and of these, 1% receive the second "hit" that leads to cancer.

Eliminating the rogue cells before cancer develops, is too aggressive a treatment to be considered which also means screening is unlikely.

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

Study leader Professor Tariq Enver, from the Medical Research Council Molecular Haematology Unit in Oxford, says these are the cells which dictate the course of the disease and now they have identified them they can hopefully be targeted.

Professor Mel Greaves, from the Institute of Cancer Research and co-author on the study, says the study in the twins had been unique but he suspects the stem cells might escape conventional chemotherapy and cause relapse.

Professor Greaves says they still have to figure out why it happens in one child and not the other but they suspect it was triggered by a common childhood infection.

Experts say while 90% of children now survive leukaemia because of intensive chemotherapy, that comes at a price; after her cancer treatment Olivia was left unable to fight a chicken pox infection and lost her sight in one eye; she remains in remission from the leukaemia.

They say a significant number of children are now being over-treated and in future, maybe children will be tested to see if the stem cells had been killed off after the first few weeks of chemotherapy which might spare many the harmful side-effects of treatment.

The experts believe that by identifying the cells involved, children at risk of relapse will hopefully be spotted and new, targeted drugs to treat the disease developed.

The study is published in the current issue of the journal Science.