East Montgomery Times

Researchers at the Children's Hospital of Philadelphia (CHOP) have uncovered a new side effect of Acute Myeloid Leukemia (AML) that impacts healthy blood-forming stem cells. This discovery, with potential long-term implications, was published in Cancer Letters. AML, known as the second most common blood cancer in children, has been found to leave a lasting mark on these stem cells, affecting immune responses even after the disease is in remission.

According to Ding-Wen Chen, PhD, inflammation is a common feature of cancer, where both cancerous cells and the surrounding bone marrow environment emit substances that trigger inflammation. This phenomenon is noted to substantially decrease survival rates across various age groups, particularly in children. The origins of this inflammation have been largely understudied. A previous study by CHOP and the University of Pennsylvania, published in Leukemia, indicated that AML cells could initiate inflammation in long-lived stem cells, which play a crucial role in producing blood and immune cells throughout life.

In a follow-up study, researchers led by Ding-Wen Chen explored these effects using a preclinical model. They merged healthy blood-forming stem cells with genetically modified ones that could develop into AML and later achieve remission. The findings revealed that when exposed to AML cells, the genetic activity of healthy stem cells changes. This change results in a reprogramming effect that persists even after cancer remission, causing prolonged alterations in inflammation and metabolism. This enduring inflammation in stem cells could potentially lead to serious health issues affecting other organs.

"This is the first report of an innate immune memory of the cancer exposure in healthy stem cells," stated Peter Kurre, MD, a senior study author and Director of the Pediatric Comprehensive Bone Marrow Failure Center at CHOP. "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."

The research team aims to investigate methods to reset or reprogram stem cells affected by AML. The study highlights the importance of approaches to cancer remission that address not only the elimination of cancer but also the management of its lasting effects on the body.

The research received support from Alex's Lemonade Stand Foundation for Childhood Research, 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.