The email that Kyle Brownell sent to Emily Heikamp, MD, PhD, in October 2021 was a plea for a lifeline. His then 19-year-old son, Andrew, had already undergone a stem cell transplant to treat a rare type of leukemia, but just six months later, he was facing a recurrence. The future seemed unclear.
“I was at the bottom,” Andrew recalls. The kind of leukemia he had, known as NUP98-rearranged acute myeloid leukemia (AML), grows rapidly and because of its rarity, his physicians in Minnesota weren’t sure how to treat it after it proved resistant to the stem cell transplant. They were recommending another transplant, but the arduous process was fresh in Andrew’s mind. The treatment, which requires intense regimens of chemotherapy to kill bone marrow cells before resetting the immune system with a transplant, had been exhausting and complicated.
During treatment, though, his father dedicated himself to understanding AML and its treatment. Andrew can recall nights when he’d wake up in his hospital bed, and his father would be poring over papers.
“It was great for me,” Andrew says. Kyle was often the one asking questions, looking for providers, and ensuring that they were making the most informed decisions. “While I was going through treatment, I just didn’t have the bandwidth. I depended on him. I didn’t have to worry about the level of care I was getting. He did that for me.”
After the news of the recurrence, Kyle’s research brought them to an expert at a cancer center in Texas where multiple AML-related trials were being offered. Andrew’s doctor in Texas handed him a copy of a recently published study from Dana-Farber led by Heikamp and Scott Armstrong, MD, PhD, exploring whether NUP98-rearranged AML was responsive to a type of drug called a menin inhibitor. The results were incredibly promising, and the drug had just been approved for a clinical trial a month prior to the Brownells’ visit to Texas.
Kyle emailed Heikamp because he felt like he needed to understand the science behind the drug before they entered the trial. His family was running out of options. Even with a second transplant, Andrew faced low odds of survival.
“I actually still have the email,” Kyle says. “I felt like the more educated I was, the better questions I could ask.” Heikamp responded just half an hour later.
Targeting the foundation of AML
As a post-doctoral fellow in Armstrong’s lab, Heikamp had been searching for new targets for NUP98-rearranged AML. By then, Armstrong and his team had already established that a protein called menin was driving certain leukemias. These leukemias share a stem cell-like gene expression that causes cells to divide rapidly and uncontrollably. In this setting, menin cooperates with certain proteins that keep these cancer-causing genes turned on.
Working off this information in 2019, Armstrong’s lab was able to demonstrate for the first time that a menin inhibitor – a precursor to the now-FDA-approved revumenib – was an effective treatment for AML with fewer side effects than traditional chemotherapy.
“What fascinated me about the drug is that it was targeting the direct driver of the disease,” says Heikamp. “Removing menin from these large protein complexes that are parked on DNA at cancer causing genes was like taking the bottom block out of the Jenga tower.”
Armstrong and Heikamp theorized that menin inhibitors could treat other types of AML if the proper proteins were targeted. Heikamp set about looking for one and landed on NUP98-fusion proteins, which are produced by a rearrangement of the NUP98 gene. Although it’s a rare characteristic overall, it’s the most common driver for children with chemotherapy-resistant leukemia.
It took years of work to build the scientific rationale that would later enable patients like Andrew to enroll in menin inhibitor clinical trials. When Heikamp started, there were no commercially available models of NUP98-rearranged AML that Heikamp could use to test menin inhibitors in the lab. Instead, she needed to build her own cell lines and patient-derived models in mice, before she could test the efficacy of menin inhibitors in NUP98-rearranged AML.
At the same time, she was navigating a pandemic and became a mother to her first child. “It was a lot to navigate, but with the help of my mentor Scott Armstrong and everyone in his lab, we were able to accomplish this work,” she recalls.
When she became a cancer researcher, Heikamp never expected to directly witness the impact of her efforts. A mentor once compared cancer research to laying bricks in a foundation – one small discovery provided a foundation for the next. Heikamp was content to simply contribute to the next generation’s discovery.
A promising future
But her research became a lifeline for Andrew and his family. Within a month of starting treatment, his blasts (or young white blood cells that are a marker for leukemia) had disappeared from his blood, and his normal blood counts started to return. A second stem cell transplant was successful, and Andrew returned to Minnesota’s St. Thomas College to study biochemistry. Over the years, Heikamp and the Brownell’s have stayed in touch. The family toured Armstrong’s lab in Boston in 2023, and in 2025, Heikamp joined the Brownell’s to watch Andrew graduate. She still gets emotional thinking about his progress.
“It’s really why we all get up in the morning,” she says. “We want to see our work impact a patient. I never thought I would see it.”
Heikamp’s support has touched both Kyle and Andrew. “Dr. Heikamp got paid nothing to be my friend,” Kyle says. “Her correspondence was truly a lifeline.”
Her support and the attention of many other clinicians inspired Andrew. He is now attending graduate school to earn his physician assistant degree. He remains cancer free and credits much of that to his father’s tireless work.
“It took someone like my dad to connect people and pull resources together,” Andrew says. “It was like having a personal doctor.”
He did not realize it at the time, but Andrew was one of the first people to take this drug which has researchers enthusiastic about further applications. Heikamp and her team are exploring other potential targets in NUP-98-rearranged leukemias which are similar to menin. These so-called KAT inhibitors can also turn off cancer causing genes. Just last year, in collaboration with researchers at St. Jude, Heikamp and Armstrong found that KAT inhibitors have a synergistic effect when used in combination with menin inhibitors
“One plus one doesn’t just equal two in this situation,” Heikamp observes. “It equals four.”
Looking back, Kyle is both grateful and in awe about their contribution. “We’re thankful we could be part of hopefully paving the way for a lot of others to get a cure,” he says.