Acute lymphoblastic leukaemia is a type of blood cancer that constitutes 25% of all cancer diseases in children. Each year the disease afflicts several thousand children in Europe. The causes of this type of leukaemia are unresolved, and therefore researchers are working intensely worldwide to identify these causes. The new study reveals part of the mystery.
Presumably, leukaemia arises in an interaction between the different types of damage that can occur in the genetic material of cells (i.e. mutations) and infections or other impacts on the immune system in early childhood. Mutations in the genetic material change the behaviour of the cells which then grow and spread uncontrollably.
In the chain of billions of building blocks that make up human genetic material, there are millions of differences between two random individuals. This is why we all look different, why our bodies work differently (e.g. that we have different blood types), and also why two children do not have the same risk of developing leukaemia.
In Denmark, the study is headed by Professor Kjeld Schmiegelow from the Department of Paediatrics and Adolescent Medicine at the Juliane Marie Centre at Rigshospitalet and by Associate Professor Ramneek Gupta from the Center for Biological Sequence Analysis (CBS) at DTU Systems Biology.
"The congenital variations in the patients' genetic material which turned out to be associated with the risk of developing leukaemia as a child are located in an area that is often affected by new mutations in cancer cells. Thereby, the new findings emphasise that development of cancer should not only be seen as a result of new mutations that affect the genetic material, but as an interaction between variations in the genetic material the child is born with, and new damage that arises later in life." explains Professor Kjeld Schmiegelow.
The congenital variations in the genetic material found by the researchers occur in 6% of the children with leukaemia in the study, and they were associated with a 2-3 times higher risk of developing leukaemia. In the Danish part of the study, Rigshospitalet and DTU Systems Biology were responsible for collecting data and for analysing the genomes of the children in the study.Danish control children were selected from The Danish Childhood Obesity Biobank in collaboration with Torben Hansen and Jens-Christian Holm from University of Copenhagen and Copenhagen University Hospital Holbaek.
The large amount of data required collaboration between DTU and Rigshospitalet on collecting and analysing the data.
"At CBS at DTU Systems Biology we have Denmark's largest super computer,Computerome, which is also optimised for life sciences research. This means that by using complex algorithms, we can quickly find patterns in the large volume of data. Some of the more complex analyses will be included in future publications, and we're obviously looking forward to this," explains Associate Professor Ramneek Gupta form CBS and DTU Systems Biology.
The researchers stress that the results do not mean that we now can now predict whether or not a child has a high risk of developing leukaemia, but the results are an important step on the road to understanding why leukaemia occurs.
Read the article Inherited Coding Variants at the CDKN2A Locus Influence Susceptibility to Acute Lymphoblastic Leukemia in Childrenin Nature Communications.