Genetics of leukaemia relapse revealed

Scientists have uncovered key genetic changes in the cancer-causing cells when childhood leukaemia recurs. It is hoped that the findings can be used to help beat the disease.

Acute lymphoblastic leukaemia (ALL), a cancer of the blood and bone marrow, is the most common form of childhood cancer. Eighty per cent of children with the disease are cured, but of those that suffer a relapse, only 30 per cent survive.

In their study, researchers at the St Jude Children's Research Hospital in Memphis, Tennessee, US, analysed the genes in the cancer cells of 61 children with ALL when they were initially diagnosed, and then compared them to the genes after they relapsed. By examining copy-number variations (lengths of DNA that are lost or duplicated) they found that only six per cent of relapses were caused by new cancers. In 42 per cent of patients, cells causing the relapse were direct descendents of the cancer cells identified at initial diagnosis. In 52 per cent, however, the relapse was caused by ancestors of the original cancer cells that were not detected when the patients were initially screened.

The work, published in Science, reports that the genetic changes were found to affect the biological machinery of B cells (white blood cells) as well as tumour suppression genes, but were rarely found to affect the genes controlling response to treatments.

'The key finding', explains Dr James Downing, one of the study's authors, 'is that in the majority of cases, relapse is arising from a cell already present at time of diagnosis. That cell is selected for during treatment and then subsequently emerges as a basis for relapse'.

The hope is to create more sensitive detection techniques to pick up the variants of the cancer cells, and create drugs that interrupt the changed genetic pathways, thereby disrupting the process of relapse. 'You've got to get them at the time of diagnosis, you can't wait till the patient relapses', said Dr Charles Mullighan, the co-author.

Mel Greaves works on ALL at the Institute of Cancer Research in London. He describes the work as 'elegant' and the clearest picture of relapse yet, but says that 'the clinical relevance of the biology is up in the air' due to the study missing out important clinical data. Downing says that there is further data to be published in the New England Journal of Medicine that will help doctors predict whether a particular patient's treatment will be successful.