A discovery hailed as a breakthrough in cancer research began, not in a laboratory, but with a 2-year-old boy who woke up from a nap one day feeling sick.
Thanks to the persistence of a pediatric oncologist in Grand Rapids, Michigan, and the research know-how of scientists in San Francisco, the boy’s illness led to the discovery of a new mutation in a cancer-causing gene.
The findings, reported in the journal Nature Communications, shed light on a gene believed to be involved in 30 percent of all cancers.
And for the little boy, the findings meant he did not have an aggressive form of leukemia. He is now an active 6-year-old, focused on coloring, not chemo.
“As so often happens, our young patients can be our most important teachers, when we all keep open and inquisitive minds,” said James Fahner, MD, division chief for pediatric hematology and oncology at Spectrum Health Helen DeVos Children’s Hospital.
David Dickens, MD, the boy’s physician, said the case takes medicine a step closer to understanding the genetic origins of illness and targeting the cause.
At the center of the study is a boy from West Michigan, who went to his doctor because he appeared to have breathing problems and a possible sinus infection. An examination revealed an enlarged liver and spleen as well as a rash. Blood tests showed low white blood cells and platelets.
Doctors told his parents that he might have leukemia. They referred his case to Dr. Dickens, a pediatric hematology-oncology specialist at Helen DeVos Children’s Hospital.
Many of the boy’s symptoms fit the diagnosis for junior myelomonocytic leukemia, a rare and aggressive disease that is treated with a stem cell transplant. Even with treatment, five-year survival is about 50 percent.
But the boy did not fit all the criteria for the disease. Bone marrow tests did not show any form of cancer. Before he ordered chemotherapy, Dr. Dickens wanted to be certain of the diagnosis.
“We don’t want to send him down that path if it’s not needed,” he said.
Intuition and science
He suspected the boy’s illness did involve the same gene that causes the leukemia.
The gene, which controls growth, is part of the RAS gene family that is the focus of a National Cancer Institute research project. Mutations in the RAS genes drive a third of all human cancers.
A Stand Up to Cancer dream team was formed specifically to investigate the KRAS gene—the one Dr. Dickens suspected in the boy’s illness.
He compares the gene to the accelerator on a car. “Where there is a mutation in it, it’s like having your accelerator stuck. It just drives. You can’t stop it from growing,” he said.
Using a microscope to examine the boy’s monocytes—a type of white blood cell—Dr. Dickens noticed they “just didn’t look right.” What he saw led him to suspect a mutation in the KRAS gene.
Dr. Dickens asked the boy’s parents if he could consult genetic experts, and they agreed.
He contacted researchers at University of California in San Francisco who agreed to look into it. He shipped blood and bone marrow samples to them.
They discovered a mutation that had not yet been found, and they determined how it affected cell growth.
In Dr. Dickens’ words, “They scienced the heck out of it.”
What they found was that the genetic mutation the boy possessed caused blood cells to continue growing—but not turn into cancer. The gas pedal was not stuck to the floor.
Because he did not have leukemia, the boy did not receive cancer treatments. Dr. Dickens continues to monitor him closely.
Although he still has a swollen spleen and low blood counts, he is a happy, high-energy boy, his mother said. He loves to read and play soccer and plans to be a doctor when he grows up.
“You would not know anything was wrong with him,” she said.
Dr. Dickens said the case shows the value of “team science.”
Researchers and physicians tend to operate in silos, separated by geography and mission. But the solution to this genetic mystery required the combined efforts of clinician and scientist, from Grand Rapids and San Francisco.
Also contributing to the effort was Aditi Bagchi, MD, a fellow in pediatric oncology and a graduate student researcher at Van Andel Institute. She communicated with the researchers in San Francisco and conveyed the findings to the boy’s medical team and family.
“It was very exciting,” she said. “The more we know about this biology, the better. And it is better not just for West Michigan and this patient. It is better for patients in general.”
Besides furthering the understanding of cancer biology and treatment, Dr. Dickens hopes the study will help identify other patients with the same mutation. And as more are identified, doctors will be able to determine what to expect—including whether it could ever “flip the switch” and become leukemia.
“It would be super-nice to have a collection of hundreds of kids with this mutation and to tell families they don’t have to worry about this turning into a bad form of leukemia,” he said.