Trending with Impact: Down Syndrome Study Leads to Potential New Interventions for Leukemia

A recent study discovers new potential target mechanisms for leukemia treatments found in a novel study of down syndrome endothelial cells.

Researcher and microscope

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Researchers from the Northwestern University Feinberg School of Medicine, Stanley Manne Children’s Research Institute, the Russian Academy of Sciences, and ARTEC Biotech Inc. were encouraged to learn more about the mechanisms involved in the increased risk of leukemia for people with down syndrome and how they also correlate with lower tumor expression.

Previous studies have found that people with down syndrome present with a unique cancer profile. Their genetic material makes them vulnerable to certain cancers, such as leukemia, however, they also exhibit measurably lower tumor expression. The researchers in this study speculated that this differentiation takes place largely in the endothelial cells

Endothelial cells support stem cell potential, promote immune system processes, and are also known to be exploited in instances of tumor proliferation. The researchers proposed that, given endothelial cells are impaired by down syndrome, they may be capable of pointing to the mechanisms involved in reduced solid tumor growth.

Genes Expressed in Down Syndrome Endothelial Cells Surprise Researchers

Initially, the team believed that the developmentally and functionally impaired down syndrome endothelial cells may be impacted by alterations in the T21 gene, located on Chromosome 21 (those with down syndrome were born with an extra copy of Chromosome 21), where many cancer-related genes have been identified over the years.

“Previous studies have shown that T21 has the potential to induce endothelial dysfunction as early as the progenitor stage, but the extent of this biological impact varies between DS [down syndrome] individuals.”

To explore this hypothesis, the researchers performed the first in vitro study of induced pluripotent endothelial down syndrome cells compared to normal endothelial cells. This method was designed to enable the team to evaluate the observable traits and genetic implications of the T21 gene in down syndrome endothelial cells. To their surprise, the study analyses revealed that the majority of the genes recorded as significantly up- or down-regulated were not located on Chromosome 21.

Using microarray, RNA-Seq, bioinformatic analyses, and functional assays, the team identified a particular set of 14 genes expressed in this environment that introduce the possibility that endothelial cells may be regulated by T21 through genome-wide alterations, as opposed to Chromosome 21-specific gene expression. They found that down syndrome endothelial cells have decreased proliferative and migratory capability, a potentially prolonged inflammatory state, down-regulated genome-wide tumor-associated oncogenes, and up-regulated genome-wide leukemia-associated oncogenes.

Conclusion

Researchers believe the expression of the genes they identified are associated with the elevated inclination toward leukemia and have a role in stunting tumor growth in down syndrome patients with leukemia. These findings also highlight the potential use for these genes as therapeutic targets in translational cancer research.

Oncotarget is a unique platform designed to house scientific studies in a journal format that is available for anyone to read – without a paywall making access more difficult. This means information that has the potential to benefit our societies from the inside out can be shared with friends, neighbors, colleagues and other researchers, far and wide.

Click here to read the full scientific paper, published in Oncotarget.

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