Mutations linked to relapse of childhood leukaemia for first time

7 Feb 2013
Mutations linked to relapse of childhood leukaemia for first time

by ecancer reporter Emma Campbell


Fresh hope may be on the horizon for many children with acute lymphoblastic leukaemia (ALL).


Scientists have identified mutations in a gene called NT5C2 that may be responsible for stopping the disease responding to chemotherapy.


ALL is the most common childhood cancer, accounting for more than 25% of all childhood cancer cases.


In ALL, the body's bone marrow produces an abnormally large number of white blood cells.


Most children with this disease can be cured, but, in 10-20% of children, the disease comes back.


Until now, researchers have been baffled trying to work out why and how ALL recurs in these children.


Through their findings on the NT5C2 gene, the authors of the current study have started to unravel this mystery.


Their findings may even help doctors to identify children who are likely to relapse, so that they can tailor their treatment accordingly.


In this latest study, published in Nature Genetics, the researchers analysed multiple bone marrow samples from 10 children with ALL to find out which genes were active in the cancer cells.


They analysed bone marrow samples from each patient at three time points: at diagnosis, during remission, and upon relapse.


By comparing the set of active genes at these three distinct time points, the team found that each patient acquired one or more mutations over the course of the disease.


In total, the team found 20 mutations that were associated with relapse of childhood ALL.


Amazingly, none of these 20 mutations has previously been implicated in ALL relapse.


The researchers noted that two patients had a mutation in the same gene, called NT5C2.


And they knew that this gene was involved in the breakdown of an important class of drugs (called purine analogues) used in ALL therapy.


The researchers went on to analyse the NT5C2 gene in 61 other children with relapsed ALL.


They found five more mutations in the gene, all of which they believe will make NT5C2 even more powerful in breaking down chemotherapy drugs, thereby making the cancer cells more resistant to treatment.


Dr Carroll says the team are planning to “test the feasibility of screening patients” to see if they can detect mutations in NT5C2.


In the future, this could provide a means for doctors to identify which children with ALL are likely to relapse.


Armed with this knowledge, it might then be possible for them to change the treatment regimen of these children so their tumours never have the chance to become resistant to treatment.



JA Meyer, J Wang, LE Hogan, et al. Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia. Nat. Genetics. doi: 10.1038/ng.2558