Acute myeloid leukemia (AML) is a relatively rare type of cancer characterized by a rapid growth of abnormal white blood cells that accumulate in the bone marrow, interfering with the production of normal blood cells. It accounts for roughly 1 percent of all cancers in adults and about 15 to 20 percent of childhood leukemia cases, according to the American Cancer Society. While AML is an aggressive disease, early diagnosis and personalized treatments are crucial to improving patient outcomes.
Emily Heikamp, MD, PhD, a physician-scientist at Harvard Medical School, Boston Children’s Hospital and Dana-Farber Cancer Institute, is making strides in better understanding what drives AML. Often, this type of cancer is caused by rearrangements within DNA structure, which can lead to two proteins wrongly joining into what is called an oncogenic fusion protein. Sometimes, these fusion proteins can cause other cells to grow uncontrollably and cause cancers, including AML.
Heikamp and her colleagues closely examine whether certain oncogenic fusion proteins might be targets susceptible to a medicine, spurring the development of new treatments for patients with AML.
“The goal is to understand the fundamental mechanisms by which oncogenic fusion proteins drive dysregulation in cancer in order to determine how to best treat patients,” Heikamp said.
For her work. Heikamp was named a 2023-2024 recipient of the ASH Peter Steelman Scholar Award, offered in partnership by Deerfield Management, the Deerfield Foundation and the American Society of Hematology. She was honored on June 18 at the AML Summit at Cure, which is an affiliate of Deerfield Management.
Efforts to Halt Progression
Some of Heikamp’s recent work suggests that a novel therapy targeting a specific fusion protein called NUP98 can halt the progression of AML and force leukemic cells to undergo a process called differentiation. When this happens, the cells adopt features of a mature white blood cell and lose their cancer potential. Her preclinical research appeared in the peer-reviewed journal Blood in February 2022.
“The impact of this research could be significant for relapsed and refractory patients whose AML disease does not respond to conventional chemotherapy,” Heikamp explained. Therapies targeting fusion proteins and their interactions may also be beneficial for patients who have already experienced toxic side effects from standard chemotherapy, she says.
The investigational therapy targeting NUP98 oncogenic fusion protein activity is a type of epigenetic drug, which are chemical compounds that change the instructions cancer cells follow by shutting down genes that drive cancer and restoring normal cell function. This drug design is expected to make a big impact in the AML space in the future and will likely pave the way for the development of combination therapies, according to Heikamp.
Facing the Scientific Challenges
Heikamp says the most rewarding and challenging aspect of her work is the same. “It all comes down to the process of scientific discovery,” she said. “Elucidating something fundamental about human disease that has yet to be discovered is a huge thrill.”
On the other hand, Heikamp noted, “Nature does not reveal its secrets readily, so as rewarding as the process of scientific discovery is, it’s also punishing,” adding she has had many failed experiments as well.
Yet she admitted that if every experiment succeeded, she wouldn’t be asking hard enough questions. “One has to be bold and take risks, and there’s a huge chance of failure inherent in the process,” she said. “When experiments reveal new insights into disease that hold the power to change a life or improve the outcome for a patient, there’s no greater satisfaction that can be had.”