High HMGN1 levels drive leukemia in Down syndrome

A genetic cause of the link between Down syndrome and B cell acute lymphoblastic leukemia (B-ALL) in both mice and human cells is reported in a paper published online this week in Nature Genetics. The study identifies a promising drug target to treat B-ALL in Down syndrome.

People with Down syndrome are at a 20-fold risk of developing a type of B-ALL, an aggressive cancer of the white blood cells. David Weinstock and colleagues found that having three copies of a small region of 31 genes on chromosome 21 was sufficient to drive the cancer. Using a combination of experiments in mice and human cells, they found that increased levels of a specific protein, HMGN1, turns on the group of genes needed for the cancer to spread. The increase in HMGN1 levels was specific to Down syndrome B-ALL, but not other types of ALL.

The authors speculate that drugs that inhibit HMGN1 could prove useful for treating B-ALL in Down syndrome patients.

doi: 10.1038/ng.2949

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