As the body ages so does the blood, raising the risk of leukemia and other blood cancers. A recent Wilmot Cancer Institute discovery showed a new way in which blood degrades when inflammation collects in the bone marrow, prompting unwanted changes in blood stem cells.
Understanding this cascade of events in the marrow, where blood is made, allows scientists to investigate the best ways to keep blood “young” and prevent cancer from developing, said Benjamin Frisch, Ph.D., research assistant professor at the Wilmot.
“If we know the instigating steps in the aging of blood stem cells,” Frisch said, “we can find ways to rejuvenate blood and reduce the risk of leukemia.”
The research could have implications for all types of blood disorders and inflammation that occurs with aging, but it is specifically directed at acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), which usually occur in adults older than 65. There is no cure for either cancer, and the five-year survival rate for AML is only 28 percent.
Frisch is co-lead author of the paper, published by JCI Insight, with Corey Hoffman, Ph.D., a former graduate student in the lab of corresponding author Laura Calvi., M.D. She is a professor of Hematology/Oncology and co-leader of Wilmot’s Cancer Microenvironment research program.
The findings emerged from collaborative work among many scientists in the Cancer Microenvironment program and Wilmot’s Hallmarks of Cancer basic biology research program. The Calvi lab for years has been investigating how to reverse damage to blood production; the latest study offers an important framework to further explore therapies to aid in healthy blood production and to potentially prevent inflammation.
The team discovered that a well-known inflammatory protein called Interleukin 1B is a key component in disrupting blood production in mice. Interleukin 1B becomes abundant in the bone marrow in response to a defect in a type of immune cell called a macrophage. The defect breaches the aging blood stem cell population — adding turmoil to a system that is already less efficient due to aging. The blood system transports oxygen and supports all of the body’s tissues and organs.
The research also provides more evidence that undesirable changes to stem cells occur in the surrounding microenvironment, an important area of focus for Calvi’s lab.
Several branches of the National Institutes of Health, including the National Cancer Institute, funded the research, as well a seed grants from Wilmot and the UR’s Clinical Translational Science Institute (CTSI) incubator fund.