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Unwinding the helix: using genetics to treat childhood cancer

Scott Supplesa
Washington University’s Todd Druley uses a magnet to separate DNA-coated magnetic beads from a liquid reaction buffer, to isolate specific genes from patient DNA for sequencing analysis.";

Pediatric leukemia is a cancer of the blood and bone marrow. There are about 3,000 new cases in the United States every year, typically in children between the ages of four and six.

With treatment, about three-quarters of affected children are able to beat the disease.

But for those with what’s known as “high risk” leukemia, the odds of survival are much worse.

Washington University pediatric oncologist Dr. Todd Druley has been trying to use genetics to understand why some leukemia is so hard to treat. He spoke with St. Louis Public Radio's Véronique LaCapra.

DRULEY: When I was training to be a pediatric cancer specialist, we had to tell families that their children had cancer, or leukemia. And it struck me right away that almost every family would ask you the same two questions.

And the first question was always, is my child going to live or die? And, while there’s no guarantees, we have 30 or 40 years of good research that we can use to give an approximate answer, and hopefully provide some insight to that question.

But the second question was much more frustrating. And it was, “Why did this happen to my child? My child’s always been healthy.” The mother and the father are almost always healthy, these cancers don’t seem to run in families most of the time, and so it comes as a bolt of lightening out of the blue.

And here in the 21st century you’d think we’d be able to say directly this is why your child got cancer, but that’s just not the case.

LACAPRA: And so tell me about your research, how have you gone about trying to find an answer?

DRULEY: Well, we’ve had a revolution in the last five years in the United States with DNA sequencing.

We often think of cancer being caused by something that is acquired. Whether someone’s smoking, or they’re sun-tanning, or they live next to toxic waste, who knows what it is, but there’s something causing a change in them.

But what we know is that these children almost never have those types of circumstances.

So why do we see so many four and five-year-olds getting cancer?  So, it makes us think that there could be things that they’re born with, not things that they acquire, that are predisposing them to getting cancers, or affecting their ability to be treated appropriately.

LACAPRA: What have you done so far to try to address this?

DRULEY: Because there’s only a few thousand of these cases every year in the United States, we’re part of the Children’s Oncology Group, which is a national consortium of pediatric cancer centers.

And I’ve asked them to provide me with hundreds of DNA samples from children that had high risk leukemias.

And we found two genes that were very important for metabolizing the drugs that we give children with leukemia — steroids, and another class of drugs called anthracyclines — they had more mutations in those genes than the healthy children.

And these were genetic changes that they were born with, these weren’t genetic changes acquired in the leukemia.

And the important point here is that the children that had these genetic changes tended to die more quickly because they had exceptionally aggressive leukemia.

LACAPRA: And so how can we use this information to actually help children who have leukemia?

DRULEY: Well, we’re at the cusp of using DNA sequencing as a typical lab test. So, just like an x-ray, just like a blood test, we’re right at the beginning where we can simply order DNA sequencing of any number of genes.

So with the information that we have today, we could suggest that these children don’t need to go through months and months of intensive chemotherapy. It might be most appropriate to send them straight to bone marrow transplantation.

And bone marrow transplantation we know is most successful when children are at their strongest and healthiest, because it is an intensive procedure.

So if you can spare them months of really intense treatment, and take them directly to bone marrow transplant, we would expect that their outcomes would be much better than they have been historically.

Now in the meantime what we’d like to do is try to understand how these genetic changes alter proper drug metabolism, and then design a treatment — a very à la carte type of a strategy — and say based on your genetics, these are the five or six medications that are going to be most efficacious for you. And I don’t think we’re that far away from being able to do that.

Now whether that translates into higher cure rates remains to be seen, but I’m hopeful.

Follow Véronique LaCapra on Twitter: @KWMUScience