Analyses of cell toxins in blood samples from 270 South American and Asian children with leukaemia have been studied at BonkoLab, the child cancer laboratory at Rigshospitalet, in connection with a large international study of child leukaemia recently published in the prestigious Nature Genetics.
“One of the main conclusions of the study is that different ethnic groups have different genetic variants in their genome, depending on whether they have Asian, South American, African or European roots, for example, and this can determine whether they’ll have a good and successful course of chemotherapy. Therefore, when developing personalized medicine, there’s no point in just finding the most frequent and most important variants in the genetic material of people from Western countries. This’ll be far from adequate to ensure that the medicine is suitable for Danes whose ancestors have another ethnic origin,” explained Professor Kjeld Schmiegelow, a consultant at the Department of Paediatrics and Adolescent Medicine.
It is no accident that Rigshospitalet has been responsible for the analysis work in the study. Rigshospitalet is the only place in the world where it is possible to carry out the special DNA thioguanine-nucleotide analysis which can show cells’ ability to assimilate and absorb an important cell toxin (6-mercaptopurine) used in treatment. Such analyses enable physicians to determine the strength of the dose an individual patient can tolerate.
React to treatment differently
Every year, BonkoLab performs tens of thousands of cell toxin analyses for Nordic children with leukaemia, in order to ascertain the optimal treatment for patients, and several of these analyses cannot be performed anywhere else in the world. If the treatment intensity is too low, there is a risk of relapse, and if the dose is too high, there is a risk of developing a new cancer disease or of infection because of a weak immune system.
“We aim to avoid as many side-effects from the treatment as possible by adapting the treatment to the genetic material of the individual patient. However, this can only partly explain why patients react differently to the treatment. Therefore we have to measure concentrations of medicine directly in the patients’ blood. However, some patients are at risk of life-threatening side-effects if they receive normal doses of treatment. This applies in particular for groups of patients who are intolerant to the medicine because of a defect in their genes. They can benefit immensely from tailored treatment early on.”
Ethnicity and personal medicine
Science has come a long way in mapping the full human genome, including in Danish patients, and this may be a huge leap in routine patient treatment, because comprehensive mapping of patients’ DNA is no longer as expensive as it was. According to Kjeld Schmiegelow, it is just as important to identify and describe how different treatments work in relation to relevant gene variants, including how patients assimilate the chemotherapy. This also applies for the, as yet, poorly described factor; ethnicity.
“Almost all medicine is developed in industrialised countries, especially in Europe and the US, and the genes on which we usually focus often fail to explain the side-effects in treatment we observe in other ethnic groups in society. This is a serious weakness if we are to launch personalized medicine on a large scale,” he said.
American researchers from St. Jude Children’s Research Hospital have led the international research project, with participation from paediatric oncology centres in Denmark, the US, Asia and South America. The Danish part of the project has been supported by Børnecancerfonden.