Individuals with Down syndrome are at a heightened risk for leukemia. Researchers from the University of Copenhagen and Stanford University have shed light on this by pinpointing distinct alterations in blood cells found in those with Down syndrome.
Globally, approximately one in 700 children is born with Down syndrome, a condition characterized by an extra copy of chromosome 21, leading to a total of 47 chromosomes instead of the usual 46. This additional chromosome often results in unique physical traits and varying degrees of cognitive challenges.
Moreover, infants with Down syndrome frequently exhibit an increased count of red blood cells, and as they mature, they are 150 times more likely to develop leukemia compared to their peers without the disorder.
“Our research indicated that the presence of an extra chromosome 21 changes the packaging of DNA within cells. This alteration influences the regulation of specific genes, potentially playing a role in the onset of leukemia,” says Rebecca Moller, one of the researchers from the University of Copenhagen who contributed to this study.
To gain deeper insights into how the additional chromosome 21 impacts cells, researchers sequenced the genetic material from over 1.1 million cells derived from fetuses with and without Down syndrome.
“Interestingly, the dysregulations we observed are not consistent and depend on the type of cell and its surroundings. For instance, blood stem cells in individuals with Down syndrome exhibit gene dysregulations related to red blood cell production, which clarifies the symptoms seen in newborns,” notes Professor Ana Cvejic, the senior scientist from the University of Copenhagen.
Excess Cellular “Powerhouses”
Additionally, the researchers found another significant variation in the blood stem cells of individuals with Down syndrome: they possess an increased quantity of mitochondria, the cell’s energy-generating “powerhouses.”
While generating energy is crucial, an overabundance of mitochondria can be detrimental to a cell and its DNA by releasing harmful substances.
“These harmful substances, known as reactive oxygen species, can damage DNA, leading to mutations that might result in pre-leukemia or, ultimately, leukemia,” explains Dr. Andrew Marderstein from Stanford University, the lead author of the study.
The study’s results highlight the need to grasp the complex relationship between genetics and the cellular environment in the blood cells of individuals with Down syndrome.
“This research represents the largest effort of its kind and confirms that both the genetic framework and the cellular context are essential for understanding the development of blood cells and leukemia. Comprehending these mechanisms is vital for steering future studies in stem cell biology and cancer,” asserts Professor Ana Cvejic, who emphasizes that these findings enhance our understanding of disease progression in Down syndrome.
The paper titled ‘Single-cell multi-omics map of human fetal blood in Down syndrome’ has been published in Nature.
