16 September 2020

A genetic investigation into the increased risk of leukaemia among people with Down’s syndrome has provided new insights into the disease, scientists say.

People with Trisomy 21, also known as Down’s syndrome, have an increased risk of developing blood cancers including acute megakaryoblastic leukaemia and acute lymphoblastic leukaemia. However, at the same time there is a lower prevalence of solid tumours amongst people with Down’s syndrome. A team led by researchers from Lurie Children’s Hospital of Chicago, USA, set out to investigate whether endothelial cells might provide a clue to this unique clinical picture.

Mariana Perepitchka and Yekaterina Galat from of Lurie Children’s and colleagues used skin samples from two patients with Down’s syndrome to create induced pluripotent stem cells in the lab. These cells were then grown into endothelial cells, to understand the effects of Trisomy 21 on endothelial cell development and function.

During the process, the team identified a set of genes that were overexpressed, which the researchers say create an environment conducive to leukaemia. The changes in gene expression also altered how endothelial cells functioned throughout cell maturation. Full details of the research appeared in the journal Oncotarget.

The team believe that their findings could help create new drug treatments – and possibly prevention strategies – for leukaemia, both in people with Down’s syndrome and the general population.

Mariana Perepitchka said: “We found that Down syndrome, or Trisomy 21, has genome-wide implications that place these individuals at higher risk for leukaemia. We discovered an increased expression of leukaemia-promoting genes and decreased expression of genes involved in reducing inflammation.

“These genes were not located on chromosome 21, which makes them potential therapeutic targets for leukaemia even for people without Down syndrome.”

Co-author Yekaterina Galat added: “Our discovery of leukaemia-conducive gene expression in endothelial cells could open new avenues for cancer research."

Senior author Vasiliy Galat said: “Fortunately, advances in induced pluripotent stem cell technology have provided us with an opportunity to study cell types, such as endothelial cells, that are not easily attainable from patients. If our results are confirmed, we may have new gene targets for developing novel leukaemia treatments and prevention.”

Source: Perepitchka M, Galat Y, Beletsky IP, Iannaccone PM, Galat V (2020) “Down syndrome iPSC model: endothelial perspective on on tumor development”, Oncotarget, doi: 10.18632/oncotarget.27712 


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