New clue to Down syndrome, leukemia link

From Atlanta, at a meeting of the American Society of Hematology

People with Down syndrome are at least 10 times as likely as people without it to develop leukemia. Scientists now report that a mutation in the JAK2 gene on chromosome 9 shows up in one-fifth of people who have Down syndrome and acute lymphoid leukemia (ALL), suggesting that the mutation accounts for some of this increased risk. It’s the second mutation implicated in the Down-leukemia puzzle.

People with Down syndrome have an extra, or third, chromosome 21. This so-called trisomy causes the condition, and scientists have wondered whether it also predisposes to leukemia. But since most people with Down syndrome don’t develop the blood cancer, researchers assumed there were other genes involved. Five years ago, researchers reported that one-fifth of people with Down syndrome who have acute myeloid leukemia have a mutation in a gene called GATA1 on the X chromosome.

In the new study, physician Shai Izraeli of Tel Aviv University in Ramat Gan, Israel, and his colleagues analyzed blood samples from more than 8,000 childhood-ALL patients. The team found that 16 of 81 samples from patients with Down syndrome had the JAK2 mutation. The defect was exceptionally rare in ALL patients without Down syndrome.

“We think trisomy in chromosome 21 gives a survival advantage to cells carrying the JAK2 or GATA1 mutations,” Izraeli says. To a cancer researcher, “survival advantage” is a bad thing—a trait that enables a malignant cell to live on and on.

JAK2 normally encodes a protein associated with cell proliferation. A JAK2 mutation also shows up in people with polycythemia vera, which is marked by abnormal red blood cell growth. Although the JAK2 mutation linked to ALL differs slightly from the defect in polycythemia vera patients, research into JAK2 inhibitors already under way for that disease could speed drug development for ALL patients with Down syndrome, Izraeli says.

From the Nature Index

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