Iowa cancer researchers focus on white blood cell maturation, resiliency

Raquel Espin Palazon, ISU associate professor of genetics, development and cell biology, has studied what causes leukemia cells to halt their maturation into white blood cells, leading them to remain functionless and spread without dying, which makes people sick. At DMU, biochemistry and nutrition professor Elitsa Ananieva is studying certain white blood cells’ internal functions to better sustain them in the fight against cancer cells.

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Both researchers cited their fascination with the immune system and its intricacies as drivers of their work, and said they hope their reports can serve as a base for further study and eventual new treatments for those dealing with cancer. Maintaining balance in the immune system to ensure it can protect the body but not become overactive and end up hurting healthy tissue is “one of the most important aspects of staying healthy,” Ananieva said.

“The first step is to understand how nature works, how our bodies work, right?” Espin Palazon said. “And then, once we understand, we can cure disease.”

Helping blood cells mature

Espin Palazon said she’s dedicated her research career to inflammatory signals in blood cell creation. Her most current work has drilled in on a protein called progranulin, which she said is a highly expressed gene in a type of white blood cells called macrophages.

The team studied these cells and the protein in zebrafish, she said. Their embryonic development is as quick as 48 hours and they have two kinds of progranulin — one only found in immune cells. They found that progranulin is “critical to generate these mature white blood cells,” but when examining human leukemia cells to see if they would also mature with the protein, it didn’t work.

This could mean two things, she said, one being that the protein doesn’t have the same function in humans and zebrafish, or that they were missing a piece of the puzzle. After going back to further study the fish, Espin Palazon said they found that a signaling pathway must also activate in order for the cells to mature.

The signaling pathway collects information from outside the cell through chemical signals and brings it into the cell’s DNA.

“We were able to now activate those two components, progranulin and the other signaling pathway, and then we were able to see that the leukemia cells started to differentiate and to express the markers of the mature white blood cells,” Espin Palazon said.

By overcoming the blockage that stops leukemia clones from leaving their progenitor state and maturing, Espin Palazon said they are then short-lived and die, stopping them from accumulating in the bone marrow and disrupting blood production.

Leukemia is the most common cancer among children, Espin Palazon said, and she hopes that one day this treatment can contribute to increasing survival rates.

“It would be amazing to know that many kids can be saved because of that basic knowledge that we have gained thanks to the zebrafish, thanks to this model organism,” Espin Palazon said.

Creating T cell resiliency 

Ananieva’s research focused on the internal health of T cells — a white blood cell that can recognize and fight infections and tumors. She explored how to ensure the cells’ resiliency in a tumor environment that can sap their ability to function.

“T cells can recognize and destroy cancer cells, but the tumor microenvironment places them under significant metabolic stress, leading to a dysfunctional state known as exhaustion,” Ananieva said in an email. “Although these T cells can still detect the tumor, they often lose their ability to eliminate it effectively. Our research focuses on identifying metabolic interventions that can restore T-cell function and enhance anti-tumor immunity.”

Rather than zebrafish, Ananieva worked with mice genetically modified to her specifications in order to create the correct conditions for her team’s research. Certain metabolic genes were taken out of the different mouse groups’ T cells to see how they would fare against lymphoma, and the team found that tumor growth was reduced by as much as 75%.

By identifying the genes that can aid in T cell resiliency when reprogrammed, Ananieva said they can then target those areas with pharmaceutical interventions and elevate the efficacy of other cancer treatments. One such treatment is CAR T-cell therapy, where a patient’s blood is taken and their T cells engineered to attack their specific cancer before going back into the body.

Ananieva’s hope is that one day medical professionals have expansive access to the drug cocktails and treatments they need for patients based on their specific profile, what she called “personalized medicine.” This would be something all scientists could contribute to.

Some of those contributors could be the students she works with today, she said.

“One of the most rewarding things for me is seeing medical students become excited about scientific discovery. I am passionate about engaging future physicians in research because it allows them to connect basic science with patient care,” Ananieva said in an email. “It is truly gratifying to watch students become inspired by the investigative process and gain insights that they can carry forward into their medical careers, whether they are caring for patients, evaluating new therapies, or contributing to clinical research themselves.”

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