Searchers establish a link between Down Syndrome and leukaemia


Acute leukemia

It has been known for years that people living with Down Syndrome more frequently develop a certain type of cancer of the blood cells (Acute Lymphoblastic Leukaemia ALL). Until this day, no explanation had enabled researchers to understand why. A study published in the magazine Nature (ref) changes the situation.

Thanks to research on Down Syndrome, English researchers have been able to demonstrate the implication of the genes present on the chromosome 21 in the development of ALL. This study allows researchers to considerer new therapeutic clinical trials in the years to come to fight against this type of cancer.

Analysis of mouse models for Down Syndrome.

The study was carried out in three phases: the first was the analysis of the supernumerary genes of the mice “called models” for Down Syndrome. The researchers focalised on the blood cells (a type of cell called “B cell”) which cause the leukaemia. These B cells, in the mouse models for Down Syndrome, develop in an abnormal and uncontrollable way, expressing leukaemia. By analysing these B cells, the researchers observed that they were producing, in an abnormal way, certain proteins (called “PRC2). These proteins are at the origin of the multiplication of the B cells. This multiplication is problematic as the B cells have not yet reached their normal stage of development.

Searching for the connection between leukaemia and people living with Down Syndrome.

The second phase of the programme was no longer focused on mice but on men. The researchers compared the influence of many genes involved in the production of PRC2 proteins on two groups of people (one composed of people with Down Syndrome, the other with ordinary people). By comparing thousands of genes, the researchers noticed an abnormal regain of activity of those which stimulate the growth and cellular division of the B cells in the group of people with Down Syndrome. The presence of the supernumerary chromosome is therefore at the origin of the development of this form of leukaemia.

Looking for the gene responsible for the cellular division.

The third phase of research consists of trying to identify the gene responsible for this abnormal cellular division of the B cells. By isolating the various supernumerary genes in the mouse models for Down Syndrome, the researchers have been able to identify the role of the gene HMGN1 in the proliferation of the B cells. They noticed that this gene had an essential role in the proliferation of these cells: By ”shutting it down” the researchers noticed that the B cells stopped proliferating.

Conclusion of the research and future hopes.

This study enabled the researchers to understand the implication of Down Syndrome in the development of the type of cancer ALL : the overexpression of the gene HMGN1, involved in the division of the B cells, leads to a proliferation and a division of these cells which are not yet fully mature.

By studying how Down Syndrome works, this study will enable to launch, in the years to come, therapeutic research projects to fight acute lymphoblastic leukaemia. Even though no treatment is available yet, it however gives hope in the battle against this kind of cancer which can touch everyone, with Down Syndrome or not. Research on Down Syndrome serves the whole of society!

ref.: Andrew A Lane et al. Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation. Nature Genetics 2014.