Scientists Found Surprising Obesity-Leukemia Link, and Possible Way To Fight It

Obesity already raises the risk of heart disease, diabetes, and dozens of other conditions. A large new study now points to another possible danger: a link between excess body fat and a higher risk of developing myeloid blood cancers. In early animal experiments, the same team also tested a two-drug combination that substantially reduced the signs of leukemia-like disease in obese mice.

Scientists analyzed health records and genetic data from more than 440,000 people in the United Kingdom and found that higher body weight and excess belly fat came with a measurably higher risk of developing myeloid leukemia, a group of blood cancers that includes acute myeloid leukemia. Using mice engineered to carry a leukemia-linked genetic mutation, they traced a specific biological chain reaction linking obesity to runaway cancer-cell growth and showed that a two-drug treatment partly reversed the inflammatory and blood-cell abnormalities in those animals. One belongs to the same broad drug family as medicines such as semaglutide. The other blocks IL-17A, the same inflammatory pathway targeted by several FDA-approved autoimmune drugs.

Published in the Journal of Clinical Investigation, the work centers on a gene called PTPN11, which makes a protein that helps control how blood-forming cells grow and divide. Mutations in this gene are already known to drive several leukemias, especially in children. The study adds a fresh piece to the puzzle: obesity appears to make that genetic damage far worse, sharply shortening survival in mice, while the targeted drug pair eased much of that damage in preclinical tests.

How Obesity Raises Myeloid Leukemia Risk Across a Population

To understand the human side of the obesity and blood cancer link, the research team turned to the UK Biobank, a large health database holding genetic information, medical history, and physical measurements from 440,982 participants followed for a median of about 13 to 14 years. Over that stretch, roughly 6.6% of participants developed type 2 diabetes, and a much smaller share, about 0.21%, developed myeloid cancers.

After accounting for factors like age, sex, and smoking history, the data told a clear story. Each standard step up in body mass index came with roughly a 9% higher chance of developing a myeloid cancer. A similar step-up in waist-to-hip ratio, a gauge of how much fat sits around the midsection, was associated with a 12% higher risk. People who had both obesity and Type 2 diabetes carried an even higher risk, about 51% greater than lean participants without diabetes. The core links between body fat and leukemia risk persisted even after the researchers accounted for metformin, a common diabetes drug that may confer a protective effect of its own.

These associations are drawn from observational data, so this part of the research cannot establish cause and effect. Even so, the pattern held across several measures of body fat, strengthening the signal.

Beyond the population figures, the team examined genetic records from nearly 395,000 UK Biobank participants and found that people carrying rare PTPN11 mutations tended to have less lean body mass, a hint that the mutations themselves may shape how the body stores fat. They also analyzed a separate cancer database, The Cancer Genome Atlas, which covered nearly 11,000 patients outside the UK Biobank group. There, too, PTPN11 mutations were disproportionately represented among patients with high body mass, accounting for 56.86% of all PTPN11-mutated cases.

What Obesity Does to Leukemia Cells

To get at why obesity worsens blood cancer, the researchers turned to mice. They transplanted blood-forming stem cells carrying the PTPN11 mutation into genetically obese mice and compared the results with those in lean, healthy mice given the same mutant cells.

In the obese mice, the difference was hard to ignore. The mutant, cancer-prone cells expanded fast and crowded out healthy blood cells. These animals developed enlarged spleens and livers, classic signs of leukemia taking hold, along with higher white blood cell counts and a surge of immature, cancer-like cells in their bone marrow. Obese mice given the mutant cells also lived shorter lives, a median of 190 days versus 240 for lean controls.

Genetic analysis of the bone marrow showed that obesity and the PTPN11 mutation worked together to set off a cascade of inflammatory signals, led by a molecule called IL-17A. The body normally makes IL-17A to help fight infections. Here, it was doing the opposite, helping cancer thrive by promoting the development of an immune cell type that shields tumors rather than attacking them.

At the same time, the T cells that would normally hunt down and kill cancer cells were wearing out. The immune response that normally helps recognize and attack abnormal cells had become weakened. A separate analysis of blood protein levels in 50,000 UK Biobank participants who had no blood cancer at the start found a similar pattern: those with both obesity and diabetes had higher levels of IL-17A and lower levels of GLP-1R, the receptor that drugs like semaglutide act on, than people without those conditions.

A Two-Drug Combination Against Obesity-Driven Leukemia

With this chain of events mapped out, the researchers tested whether they could break it. Eight weeks after transplanting the mutant cells into obese mice, once leukemia-like disease had already set in, the animals were randomly sorted into four groups: one got a GLP-1 receptor agonist called beinaglutide by injection, one got an antibody built to block IL-17A three times a week, one got both drugs, and one got neither.

After 30 days, the combination produced the strongest results. Mutant cancer-promoting cells dropped while healthy cells recovered, signs of T-cell burnout eased, and the tumor-shielding immune cells shrank in number. Body weight, blood sugar, and the harmful fat packed around the organs all fell in that group. Enlarged spleens and livers came back down, the abnormal immature blood cells in the bone marrow contracted, and the stem cells that make healthy blood began to recover.

Genetic analysis confirmed that the pairing dialed back hundreds of genes linked to inflammation and abnormal fat handling, nudging the tissue closer to what is seen in healthy, lean animals. Either drug alone helped somewhat, but neither matched the pair. Together, the two drugs partly restored healthy blood cell production and reduced leukemia in the animals.

These results are early, and they have not been tested in people with leukemia. Still, the researchers note that both kinds of drugs already exist and are used for other conditions. GLP-1 receptor agonists treat Type 2 diabetes and obesity. IL-17A-blocking antibodies are FDA-approved for autoimmune diseases, including certain inflammatory conditions in children as young as 2. Trials targeting these same pathways in inflammatory diseases are already underway, which could eventually inform future studies in leukemia patients.

For people living with obesity, the study offers a possible biological explanation for the long-observed link with myeloid blood cancers. Whether the treatment helps actual patients is a question only human trials can answer.

Disclaimer: This article describes early preclinical research. The human findings show an association between body fat and myeloid blood cancer risk, not proof that obesity causes these cancers. The two-drug treatment was studied only in mice, in small groups over 30 days, and has not been tested in people with leukemia. Nothing here is medical advice. Anyone with questions about their weight, cancer risk, or medications should speak with a qualified healthcare provider.

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