Why Down’s Syndrome Increases Risk of Leukemia

Children with Down’s syndrome have a 150-fold increased risk of myeloid leukemia than other children. In a study published today in Cancer Cell, researchers discovered specific gene mutations that are required for the development of leukemia in children with Down’s syndrome.

“We already knew that 30% of babies born with Down’s syndrome have acquired a change in a gene called GATA1 in their blood cells. This is not an inherited genetic change, but one that occurs and will remain only in the baby’s blood cells,” says coauthor Paresh Vyas of the University of Oxford. “The abnormality in the GATA1 gene can be detected by a simple blood test at birth. Babies with an altered GATA1 gene have a predisposition to develop leukemia, and we often refer to this as ‘myeloid preleukemia.’”

Of the 30% of children with Down’s syndrome who are found to have myeloid preleukemia, only 10% will go on to develop myeloid leukemia. But until now, it was not understood why only some children with the GATA1 mutation were progressing to full leukemia while others were not.

“To answer this question, we carefully characterized the mutations in genes required for leukemia to develop,” Vyas says. “We found that additional genetic changes are required in the altered GATA1 blood cells, and these additional changes transform the preleukemic blood cells into leukemic blood cells.” In total, 43 altered genes were found.

The new discovery has practical implications. While children with Down’s syndrome are currently tested at birth for the GATA1 mutation, it may now become possible in the future to test for the additional mutations too.

“This would mean that we could identify the 10% of children who will develop leukemia more quickly and easily, and, importantly, reassure 90% of families whose children will not develop leukemia,” Vyas explains. “The identification of these genetic changes may also mean we can develop and test new treatments specifically targeting the genetic changes we now know are required by the leukemia—and so develop more targeted treatments with less side effects.”

Current treatments for Down’s syndrome children with leukemia are already highly successful, and off the back of this research, another possible drug treatment has come to light. The drug Ruxolitinib, which is currently used to treat some blood conditions, could potentially be used to treat some of the specific genetic mutations found in the study.