Meet the Girl with Gene NUP214-ABL1

When Myrrah Shapoo arrived at Columbia University Medical Center last year with a form of cancer that wouldn’t respond to chemotherapy, a team of physicians and scientists working on a new precision-medicine initiative faced their ultimate test.

by David J. Craig Published Summer 2016
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Since the PIPseq program was launched, in 2014, more than one hundred pediatric cancer patients have had their genes sequenced at CUMC. In about two-thirds of these cases, Kung says, Columbia researchers have discovered something in a child’s DNA or RNA that has helped physicians decide how to treat the patient. The researchers’ discoveries have led to children receiving gene-targeting drugs like Gleevec or Sprycel in just a handful of cases, Kung says, because there are only a few targeted therapies approved for use in children. But the genetic analyses have guided treatment in other ways. On many occasions, they have indicated that a child has a particularly aggressive type of cancer and needs unusually high doses of chemotherapy. In other instances, the analyses have motivated physicians to perform a bone-marrow transplant earlier in the treatment process than is typical.

Molecular Pathologists Susan Hsiao and Mahesh Mansukhani

Conversely, the Columbia researchers’ analyses have sometimes indicated that physicians could save a child with unusually low doses of chemotherapy, or without a bone-marrow transplant. Physicians would prefer to scale back treatment if possible, because all cancer treatments carry risks: the toxicity of chemotherapy drugs, for instance, not only cause severe short-term side effects but also increase a patient’s long-term risk of developing other cancers; and a donor’s bone marrow might be rejected by the recipient’s body, or even attack it, both of which are often fatal.

“One of the most active areas of leukemia research today is figuring out how to identify patients who require less intensive treatment,” says Kung. “Just because we’re curing 90 percent of children with ALL doesn’t mean that we accept the toxicities that we inflict in pursuit of a cure.”

It is too soon to know if any children who have participated in the PIPseq program have been cured as a result of having had their genes sequenced. This will take several years to establish, since cancer patients are generally considered cured only after having been in remission for five years or longer. One thing that can be said for certain, though, is that there are children alive today because of this program. Among them is Myrrah Shapoo. This spring, just fifteen months after she and her father first arrived at the hospital, looking for a miracle, the family received wonderful news. There is no more cancer detectable in her blood. Her physicians are cautiously optimistic that she will stay in remission, because they have examined her blood using a newer, much more sensitive diagnostic test than the one used by her Indian doctors when they initially announced that she was in remission three years ago. Her recovery seems attributable both to Sprycel and to a transplant that CUMC oncologist Prakash Satwani performed last summer, when he replaced Myrrah’s bone marrow with bone marrow from her older brother, Ruhayl. The transplant seems to have given her immune system the boost it needed to annihilate the few leukemia cells that had remained in her body.

“Right now, we’re trying to cure Myrrah Shapoo’s cancer. Then we’ll find other kids with the same subtype of the disease and treat them the same way.” — Maria Luisa Sulis

“What we can presume is that Myrrah’s immune system originally had some sort of flaw that enabled the cancer to take root and proliferate,” says Satwani, who has been overseeing her care since the procedure. “You do a transplant in the hope that the donor’s marrow is innately stronger. So far, this seems to be the case.”

The Shapoos are now living in Morningside Heights, where Ruhayl is attending high school and Myrrah, now ten, is being tutored at home. Her parents expect the family to remain in New York City for another year or two so that Columbia doctors can continue to monitor their daughter. This suits Myrrah fine. She has become close friends with several other young cancer patients. And she loves American television — especially the cooking shows, which she credits with inspiring her dream of becoming a chef when she grows up.

“Right now, I’m focused mostly on spaghetti, which my papa lets me cook Friday nights,” she says. “He wants me to be a doctor. I might do that, too. But first a chef.”

There is ultimately more than one life at stake in the effort to save Myrrah. Many other children have similar genetic mutations. How many more children with the NUP214-ABL1 gene are out there? It is impossible for scientists to know, but studies have suggested that NUP214-ABL1 is likely to be among the most common mutations carried by the 10 percent of children with ALL who still cannot be saved through traditional chemotherapy. So identifying these children, and treating them with drugs best suited for their individual cases, could have a pronounced impact on ALL survival rates.

“The development of drugs like Gleevec and Sprycel was a big deal, because they happen to target some of the most aggressive and deadly subtypes of leukemia,” says Maria Luisa Sulis. “Kids with the Philadelphia chromosome had a dismal survival rate before Gleevec was invented. And we need more targeted therapies to be invented, of course. But we also need to identify everybody who could benefit from the targeted therapies we do have. And we’re not yet doing that as well as we could.”

Sulis is now working with other members of the PIPseq team to fine-tune their procedures for identifying children with mutations whose effects are similar to those of the Philadelphia chromosome, in hopes of diagnosing them more quickly. “People often talk about curing cancer as if there is a magic pill we’ll find that heals everybody,” she says. “The reality is much messier, slower, and more incremental. Cancer is hundreds of diseases. Right now, we’re trying to cure Myrrah Shapoo’s cancer. Then we’ll find other kids with the same subtype of the disease and treat them the same way. This is how we’ll push the cure rate for pediatric ALL up from 90 to 95 percent, and so on. And this is how we’ll beat all cancers. We will cure them one by one.”

To learn more about precision-medicine initiatives at Columbia, visit

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Outstanding article. Grateful that there are so many individuals dedicated towards finding the various cures for cancer. This research is different and exciting. Talk about thinking out of the box! Thank you!

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