Too little or too much DUX4 is just right

St. Jude researchers have evidence that a protein that fuels leukemia in some children can also doom the tumor cells.

The protein is DUX4. Normally the DUX4 gene is expressed briefly during development. But the gene is also switched on in about 7% of children with B-cell acute lymphoblastic leukemia. The cells include a fusion gene that combines part of DUX4 and the gene IGH.

The IGH-DUX4 fusion gene is created when chromosomes break and re-form.

Scientists have mapped the IGH-DUX4 rearrangement in detail. They learned how the rearrangement leads to DUX4 activation. The researchers also showed that levels of the DUX4 protein influence the fate of B cells with the fusion gene.

Leukemia occurred when levels of DUX4 were “just right.” Too much DUX4 triggered the death of leukemia cells. Too little DUX4 blocked their start.

“The results suggest a vulnerability that can be explored for treatment of B-ALL patients with this rearrangement,” said Jinghui Zhang, PhD, Computational Biology chair.

Nature Communications published a report on this work.

Read the news release