Obesity may be the fuel for leukemia, according to a study led by scientists at Indiana University School of Medicine. To help many patients facing aggressive blood cancers overcome this metabolic risk, researchers have identified a potential new treatment strategy that combines common weight loss drugs with anti-inflammatory drugs. The results of this study were recently published in the Journal of Clinical Investigation.
Obesity is known to increase the risk of certain blood cancers, but researchers sought to understand exactly what changes the chronic disease causes in the body to help leukemia grow.
This study provides a fundamentally new understanding of how metabolic diseases, and obesity in particular, directly influence the development and progression of leukemia. Rather than treating obesity as a passive risk factor, this study establishes obesity as an active biological factor linking metabolism, inflammation, and cancer. ”
Dr. Ruben Kapur, director of the Herman B. Wells Pediatric Research Center at IU School of Medicine and lead author of the study
After analyzing electronic health record data from more than 440,000 people from UK Biobank and experimenting with mouse models, researchers found that obesity creates a chronic inflammatory state that promotes the proliferation of mutated blood stem cells that cause leukemia. This harmful environment is characterized by high levels of an inflammatory molecule called IL-17A and a reduction in the body’s natural GLP-1 metabolic signaling.
Remarkably, both pathways can be targeted with readily available drugs. In this study, the scientists tested a dual therapy approach involving an anti-IL-17A antibody, currently used to treat autoimmune diseases, and a drug that promotes GLP-1 signaling, which is used in some popular diabetes and weight loss drugs. They found that by combining an IL-17A blocker with a GLP-1 drug, they were able to reduce leukemia burden and improve immune function in obese mice.
“Because these treatments are already available and have established safety profiles, our results raise the possibility that they can be repurposed, alone or in combination, to improve outcomes for patients with high-risk myeloid leukemia,” said Santhosh K. Pasupuleti, Ph.D., assistant professor of pediatrics at IU School of Medicine and co-senior author of the study. “This strategy could help slow leukemia progression while improving metabolic health and restoring anti-tumor immunity.”
The research team hopes to evaluate this new treatment in clinical studies to further determine whether the combination of IL-17A inhibitors and GLP-1 drugs can safely and effectively benefit patients with obesity-related leukemia. Future research will also focus on identifying which patients are most likely to benefit from this treatment, and will investigate how it can be applied to other forms of cancer.
“The broader implications of this research extend beyond leukemia,” Kapur said. “The demonstration that metabolic dysfunction can reprogram immune responses and promote cancer progression has implications for multiple malignancies and suggests that metabolic interventions may become a fundamental component of cancer prevention and treatment.”
Pasupuleti and Kapur are researchers in the Wells Center’s Hematologic Malignancies and Stem Cell Biology Program and the IU Melvin and Bren Simon Comprehensive Cancer Center.
IU School of Medicine’s Rahul Kanumuri, Kanaka Sai Ram Padam, Bhaskar Ramdas, Lakshmi Reddy Param, Ramesh Kumar and Laura Hanelin are also co-authors of the study. Other authors include Linke Li, Satoshi Koyama, Pradeep Natarajan, and Zhi Yu from the Broad Institute of Harvard University and MIT. Chiranjeevi Pasala and Gabriela Chiosis of Memorial Sloan Kettering Cancer Center;
This research was supported by funding from the National Institutes of Health, the Riley Foundation for Children, the Ralph W. and Grace M. Showalter Research Trust, the Leukemia Research Foundation, and the Alex Lemonade Stand Foundation.
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Indiana University School of Medicine
Reference magazines:
Kapur, R. Others. (2026). Targeting GLP1R and IL17A suppresses obesity-induced leukemia in an oncogenic PTPN11 mutation-driven model. clinical research journal. DOI: 10.1172/jci202856. https://www.jci.org/articles/view/202856
