New research from Children’s Hospital of Philadelphia (CHOP) uncovered a previously unknown side effect of Acute Myeloid leukemia (AML), the second most common blood cancer in children, that leaves a long-lasting imprint on healthy blood-forming stem cells, influencing immune responses long after the disease has entered remission. The results were published recently in the journal Cancer Letters.
Inflammation is a hallmark of cancer. In patients with AML, both cancerous cells and the surrounding bone marrow environment release harmful substances that cause inflammation and significantly decrease survival rates in patients of all age groups, especially children. The sources of inflammation, however, are poorly understood and rarely investigated. Last year, researchers at CHOP and the University of Pennsylvania published an initial study in Leukemia, which found for the first time that AML cells could trigger inflammation in long-lived stem cells. These stem cells play a key role in producing a lifelong supply of blood and immune cells, meaning the effects can have long-term repercussions.
To better understand the lasting effects in this follow-up study, researchers created a preclinical model combining healthy blood-forming stem cells with genetically modified ones that can develop into AML and enter remission. The team, led by Ding-Wen Chen, PhD, a research associate scientist at CHOP, found that when healthy stem cells are exposed to AML cells, their genetic activity changes. Even when cancer goes into remission, the stem cells showed a reprogramming effect that produced long-lasting shifts in inflammation and metabolism. When stem cells are programmed for long-term inflammation, it can lead to serious health issues in other organs.
“This is the first report of an innate immune memory of the cancer exposure in healthy stem cells,” said Peter Kurre, MD, a senior study author and Director of the Pediatric Comprehensive Bone Marrow Failure Center at Children’s Hospital of Philadelphia. “Our findings open the door to potential new treatments for pediatric patients. Like immune reprogramming for CAR-T cell therapy, we could harness the stem cell immune memory response in a beneficial way, possibly reducing the risk of chronic inflammation and other long-term health issues.”
Moving forward, Kurre and his team hope to explore ways to reset or reprogram stem cells exposed to AML. The researchers note that the study emphasizes the need for an approach to cancer remission that considers not only eliminating cancer but also managing its lasting impact on the body.
This work was supported by Alex's Lemonade Stand Foundation for Childhood Research (DWC; Young Investigator Grant; 21-23996), Cure4Cam Childhood Cancer Foundation and Marshall County Childhood Cancer Awareness Corporation.
Kurre et al. “Leukemia confers a durable imprint on healthy hematopoietic stem and progenitor cells.” Cancer Letters. Online March 1, 2025. DOI: 10.1016/j.canlet.2025.217590.
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New research from Children’s Hospital of Philadelphia (CHOP) uncovered a previously unknown side effect of Acute Myeloid leukemia (AML), the second most common blood cancer in children, that leaves a long-lasting imprint on healthy blood-forming stem cells, influencing immune responses long after the disease has entered remission. The results were published recently in the journal Cancer Letters.
Inflammation is a hallmark of cancer. In patients with AML, both cancerous cells and the surrounding bone marrow environment release harmful substances that cause inflammation and significantly decrease survival rates in patients of all age groups, especially children. The sources of inflammation, however, are poorly understood and rarely investigated. Last year, researchers at CHOP and the University of Pennsylvania published an initial study in Leukemia, which found for the first time that AML cells could trigger inflammation in long-lived stem cells. These stem cells play a key role in producing a lifelong supply of blood and immune cells, meaning the effects can have long-term repercussions.
To better understand the lasting effects in this follow-up study, researchers created a preclinical model combining healthy blood-forming stem cells with genetically modified ones that can develop into AML and enter remission. The team, led by Ding-Wen Chen, PhD, a research associate scientist at CHOP, found that when healthy stem cells are exposed to AML cells, their genetic activity changes. Even when cancer goes into remission, the stem cells showed a reprogramming effect that produced long-lasting shifts in inflammation and metabolism. When stem cells are programmed for long-term inflammation, it can lead to serious health issues in other organs.
“This is the first report of an innate immune memory of the cancer exposure in healthy stem cells,” said Peter Kurre, MD, a senior study author and Director of the Pediatric Comprehensive Bone Marrow Failure Center at Children’s Hospital of Philadelphia. “Our findings open the door to potential new treatments for pediatric patients. Like immune reprogramming for CAR-T cell therapy, we could harness the stem cell immune memory response in a beneficial way, possibly reducing the risk of chronic inflammation and other long-term health issues.”
Moving forward, Kurre and his team hope to explore ways to reset or reprogram stem cells exposed to AML. The researchers note that the study emphasizes the need for an approach to cancer remission that considers not only eliminating cancer but also managing its lasting impact on the body.
This work was supported by Alex's Lemonade Stand Foundation for Childhood Research (DWC; Young Investigator Grant; 21-23996), Cure4Cam Childhood Cancer Foundation and Marshall County Childhood Cancer Awareness Corporation.
Kurre et al. “Leukemia confers a durable imprint on healthy hematopoietic stem and progenitor cells.” Cancer Letters. Online March 1, 2025. DOI: 10.1016/j.canlet.2025.217590.
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