Researchers at Indiana University identify a vulnerability in acute myeloid leukemia by targeting IL-1 inflammatory signaling, a pathway essential for leukemia stem cell survival at diagnosis and relapse.

The Leukemia study shows AML cells depend on elevated IL-1 signaling; lowering this signal reduces colony formation and the leukemia’s ability to reestablish in human AML cells.

Genetic reduction of IL-1 signaling in human AML cells leads to fewer colonies and a diminished capacity to reestablish leukemia, suggesting the pathway is critical for leukemia stem cell survival.

UR241-2 is in early preclinical development, with related compounds already in clinical trials for other cancers and immune diseases, signaling potential future testing for AML.

Related drugs are in clinical trials for other cancers and immune-related diseases, indicating a path toward eventual evaluation of UR241-2 for AML.

Key researchers include Tzu-Chieh (Kate) Ho and Reuben Kapur of IU School of Medicine, with collaborators from multiple institutions, and the study was published in Leukemia.

Collaborators include Reuben Kapur, Tzu-Chieh (Kate) Ho, and Baskar Ramdas of IU School of Medicine, along with authors from several other institutions, highlighting a multi-institutional effort.

Researchers propose integrating IL-1 pathway inhibitors with chemotherapy to improve outcomes and reduce relapse in AML.

A drug-like compound, UR241-2, was developed to block key proteins in the IL-1 pathway; in preclinical models it impaired leukemia stem cells while largely sparing healthy blood-forming cells and reduced leukemia levels in mice.

UR241-2 targets IL-1 signaling proteins, and preclinical results show reduced leukemia burden in mice with minimal impact on healthy hematopoietic cells.

The findings suggest combining IL-1 pathway inhibition with standard chemotherapy could strengthen AML treatment and lower relapse risk.