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Senior Andrea Lee (left) and sophomore Bella VanAken (right) worked on leukemia research this summer. Andrea Lee | courtesy

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.”