A research team at Iowa State University announced on July 24 the identification of two essential components involved in blood cell development, a discovery that could lead to new treatment options for leukemia. The study, led by Raquel Espin Palazon, associate professor of genetics, development and cell biology, focused on a protein called progranulin and a cellular signaling pathway known as JAK2/STAT3.
Espin Palazon said in the university's announcement that aggressive forms of leukemia disrupt bone marrow function by causing precursor cells to stall at an immature stage. "They never finish. They never become what they should be. Because they are progenitor cells, they don't really have a function and just expand and collapse our bone marrow," she said.
The research team investigated why progranulin is highly expressed in macrophages—large white blood cells responsible for removing pathogens—and found that it plays a critical role in the maturation of myeloid progenitor cells into mature white blood cells such as macrophages and neutrophils. Experiments with zebrafish showed that one type of progranulin gene expresses only in blood cells and is necessary for this process.
When researchers attempted to use progranulin to drive differentiation in human leukemia cells, initial attempts were unsuccessful. Further investigation revealed that both progranulin and an active JAK2/STAT3 pathway are required for myeloid progenitors to develop into macrophages. Espin Palazon said adding progranulin enabled leukemia cells with active JAK2/STAT3 pathways to mature: "It was super exciting to see the differentiation, that blockage in the human leukemia line being overcome... Adding progranulin, the missing component, could be a potential therapeutic target."
The study also identified two types of embryonic macrophages—only one requiring both JAK2/STAT3 pathway activation and progranulin—which may have implications for tissue repair research. "This opens up possibilities for studying and dissecting the two different types of embryonic macrophages," Espin Palazon said.
Espin Palazon emphasized that further research will be needed before these findings can translate into clinical treatments: "It usually takes a decade or more to go from the discovery side to clinical treatment, but you need to determine how our cells are doing what they are doing before you know what to manipulate to cure devastating diseases like leukemia." The study included collaborators from Children's Hospital of Philadelphia and the University of Salamanca in Spain.
