An aggressive type of blood cancer came under the scrutiny of two Hillsdale students at the University of Nebraska Medical Center this summer.
Sophomore Bella VanAken donned safety glasses and latex gloves to study acute myeloid leukemia in the lab, while senior Andrea Lee sifted through hundreds of patient charts within the confines of an office cubicle for statistical analysis.
A cancer of the immune system, acute myeloid leukemia occurs through multiple mutations in a type of white blood cell called myeloid cells. Most common in young and old populations, the specific kind of AML studied by Lee and VanAken gives patients a 26 percent survival rate at five years since being diagnosed. Within these five years, there is a 50 percent chance that patients will experience stretches of remission as physicians battle to control a cancer that becomes chemoresistant.
VanAken dove into the biological mechanism of AML by studying the dormant AML stem cells responsible for taking the patient from remission, typically seen after five years of being cancer-free.
The problem with leukemia stem cells is paradoxical: Because they do not proliferate like normal cancer cells, these cancerous cells remain untouched by chemotherapy drugs at the initial time of treatment and become chemoresistant, VanAken said.
After seven weeks of learning experimental techniques and running different tests on AML stem cells in the lab, VanAken said her last three weeks flew by after she discovered a notable increase in the ability of a frontline chemotherapy drug known as doxorubicin for killing AML stem cells if the cells had been treated with a certain molecule. This molecule prevented a specific protein, IL1RL1, from performing its normal role in cell signaling.
Pointing out this result to her supervisor, VanAken received the go-ahead to investigate the relationship between IL1RL1 and the cell’s overall rate of reproduction. Chemotherapy drugs target all rapidly proliferating cells, but the dormant AML cells escape drugs like doxorubicin and are responsible for eventually taking patients from remission, which is why researchers are particularly interested in learning how to identify the dormant cells, VanAken said.
By blocking a molecule from interacting with the IL1RL1 protein, the AML stem cells were forced to come out of dormancy and proliferate, rendering the leukemia vulnerable to doxorubicin, VanAken said.
“Bella was so awesome to work with this summer,” said Kate Hyde, assistant professor of biochemistry and molecular biology at UNMC and VanAken’s research supervisor. “What makes her results exciting is that there are drugs already in early clinical trials that target IL-33, a molecule that’s typically associated with allergies. Because these drugs are already being tested, that’s one more step that we wouldn’t have to do.”
Hyde said her research team will continue Bella’s research on IL1R1 using lab mice and hopes to continue this same line of testing using human tissue in the near future.
Lee worked under Vijaya Bhatt, an assistant professor of internal medicine at UNMC and a practicing hematology-oncology doctor who has contributed to more than 125 articles on hematology-oncology.
Bhatt asked Lee to pioneer a data-based study on patients diagnosed and treated for AML at the university’s medical center. The results of her data collection can serve the UNMC medical community as a reference for which chemotherapy treatment plans resulted in the best patient prognosis, Lee said.
“It was hard work but, in the end, very rewarding,” Lee said.
Over the course of her 10 weeks at the UNMC, Lee searched through the medical charts of 248 patients, comparing physiological factors to the intensity of chemotherapy treatment that each patient was receiving. She found that whether a patient received high or low-intensity chemotherapy was primarily dependent on their age. The effect of the patient’s preference or physician’s judgment on the level of chemotherapy prescribed was outside the scope of her study, Lee said.
“Andrea is one of the most dedicated students I have worked with,” Bhatt said. “The large dataset that she created will be used for internal quality improvement projects as well as future publications. She did phenomenal work on a very complex topic.”