New research co-led by scientists at Indiana University School of Medicine has identified a vulnerability in acute myeloid leukemia (AML). The study revealed that this blood cancer relies on a specific signaling pathway involved in the body's inflammation response. Preclinical evidence suggests that blocking this pathway with a new drug compound could weaken AML during critical stages, potentially leading to more effective and targeted treatments for the disease.
AML has a five-year survival rate of 32.9% and approximately 22,000 new cases were reported in 2025, according to the National Cancer Institute. The disease is characterized by its treatment resistance and high relapse rate. Leukemia stem cells are a key factor, as they can survive chemotherapy and subsequently regenerate the disease. The research aimed to understand the critical mechanisms these leukemia stem cells depend on at both diagnosis and relapse, and to identify potential therapeutic targets.
Published in Leukemia, the study examined leukemia stem cells from AML patients at the time of diagnosis and during relapse. Researchers observed a significant elevation in the Interleukin-1 (IL-1) signaling pathway, an inflammatory pathway involved in the immune system. When this signal was genetically reduced in human AML cells, the cells formed fewer colonies and showed a diminished capacity to reestablish leukemia.
The team also developed UR241-2, a new drug-like compound designed to block the key proteins within the IL-1 signaling pathway. In preclinical models, UR241-2 impaired leukemia stem cells while largely preserving healthy blood-forming cells and significantly reduced leukemia levels in mice. These findings suggest that targeting this pathway could strengthen existing AML treatments, such as chemotherapy, and decrease the risk of relapse.
The researchers indicated that IL-1 signaling appears to be a fundamental survival mechanism for AML across different stages, offering a persistent therapeutic target. While UR241-2 is still in early preclinical development, similar drugs are already undergoing clinical trials for other cancers and immune-related diseases. This suggests a potential path toward eventually evaluating UR241-2 for AML. Future AML treatments may integrate this strategy alongside standard chemotherapy to reduce relapse risk and improve long-term prognosis for patients.