Worldwide, about one in 700 children are born with Down syndrome, with three chromosome 21s instead of two in their DNA. In addition to morphological changes and cognitive delay, people with Down syndrome also have a much higher risk of developing leukemia, about 150 times that of a person without Down syndrome.
For the first time, a study has just understood what mechanism unites the two diseases. The presence of the extra chromosome 21 alters the way DNA is packaged in cells, which disrupts certain genes, reveals work in the journal NatureIt is this deregulation that leads to the appearance of leukemia.
DNA damaged by harmful molecules
In total, more than 1.1 million cells from fetuses with Down syndrome were sequenced. The results show that the deregulations are not uniform but depend on the type of cell and its environment. Above all, the researchers noticed that inside the cells there was a very high number of mitochondria, small structures that act as the cell's "power plant." Energy production within cells is crucial, but too many mitochondria can damage the cell.
Cell containing mitochondria (in green). Credits: SCHMITT/BSIP/AFP
In fact, mitochondria produce what are called " reactive oxygen derivatives", which are harmful to the body. " These reactive oxygen derivatives attack DNA because they are highly reactive and very unstable molecules, which seek to stabilize themselves by interacting with other molecules around them, such as DNA.", details from Science and Future Professor Ana Cvejic of the University of Copenhagen and author of this work. By attacking DNA, they cause mutations that can lead to leukemia.
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The Mystery Behind Mitochondria
For now, the excess number of mitochondria remains a mystery. It's complicated to know why people with Down syndrome have more mitochondria in their red blood cells. Many factors could be at play. It could be due to a deregulation of certain mitochondrial genes encoded on chromosome 21. It could also be due to a dysfunction at the mitochondria level, or perhaps a mixture of both.. »
This mechanism, which has now been brought to light, does not, however, allow us, at this stage, to envisage new therapies to treat the different types of leukemia that exist. Over a five-year horizon, it is estimated that the survival rate of people with Down syndrome and acute myeloid leukemia (cells that normally develop into white blood cells become cancerous in the bone marrow, editor's note) is from 80 to 90%" explains Prof. Cvejic. Five-year survival drops from 60 to 80% for people with acute lymphoblastic leukemia (which appears in blood stem cells).
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The team now wants to study in more depth the links between changes in the organization of chromatin, the structure in which DNA is packaged, and the appearance of mutations in order to better understand how leukemia develops.
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