New Research Shows Genetic Variants May Increase Leukemia Risk in Children with Down Syndrome


Researchers find 4 genetic variants that are strongly associated with the risk of acute lymphoblastic leukemia in children with Down syndrome.

Researchers have identified several genes in children with Down syndrome associated with a high risk of acute lymphoblastic leukemia (ALL), according to a study by Baylor College of Medicine.

Although the link between children with Down syndrome and ALL has been recognized since the 1950s, there is still a bit of debate as to the reason behind the association.

Therefore, the researchers conducted a genome-wide association study (GWAS) to determine whether there were genetic differences between children with Down syndrome and children without Down syndrome, and ALL that leads to an increased risk of the disease. The reasoning being that if they found cases of Down syndrome with ALL with a higher percentage of certain gene variants that were not present in children with Down syndrome who did not have ALL, then they could infer that those genetic variants may be important in developing the disease.

The research team examined approximately 500 cases of Down syndrome with ALL and more than 1000 controls, or children with Down syndrome with no ALL. They found 4 genetic variants that were strongly associated with ALL risk in children with Down syndrome. Although these variants had previously been found, there were stronger effects in the current study.

In examining 2 of these genes, researchers found that children with Down syndrome carrying a particular variant of the CDKN2A gene have a 1.7 times higher risk of developing ALL than children without Down syndrome who carried the same genetic variant.

The second gene was IKZF1, which is involved in the development of B cells, a type of immune cell that typically transforms into leukemic cells in ALL. The study authors also discovered that reducing IKZF1 expression resulted in significantly higher proliferation rates in Down syndrome than non-Down syndrome cells. Because a characteristic of cancer cells is their higher proliferation rate, these results suggest a mechanism by which changes in IKZF1 expression may contribute to developing ALL, according to the authors.

The findings of this study will serve as a framework for future assessments that researchers hope will improve outcomes among children with Down syndrome.


  • Brown A, de Smith A, Gant V, et al. Inherited genetic susceptibility of acute lymphoblastic leukemia in Down syndrome. Blood, 2019; blood.2018890764 DOI: 10.1182/blood.2018890764

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