More than 50 years after Agent Orange was used in Vietnam, a new national study has been published online ahead of print. blood progress highlights genetic changes linking exposure to Agent Orange and myelodysplastic syndromes (MDS), a group of bone marrow cancers that can progress to acute leukemia. The results of this study shed light on why some veterans develop more severe bone marrow cancers and have the hope that these people will be able to access the service-related care they need.
The study, led by Michael A. Sekeres, MD, chief of hematology at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, expands on findings he presented at the 2025 American Society of Hematology (ASH) Annual Meeting.
The first study published at ASH found an association between exposure to defoliants and the development of MDS. We now explain how the biology of the disease looks different in this exposed group. ”
Michael A. Sekeres, MD, Chief of Hematology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine
Agent Orange is a herbicide used by the U.S. military to remove forest cover and destroy crops during the Vietnam War. They often contained highly toxic forms of dioxins, chemicals that disrupt cellular processes. Approximately 2.6 million U.S. military personnel may have been exposed.
Orange defoliant has already been linked to several cancers, including certain lymphomas and multiple myeloma. Until the publication of ASH, there was limited evidence linking it to MDS.
MDS develops slowly, usually late in life. Most people are diagnosed in their 70s. The long time between exposure and diagnosis makes studying environmental risk factors particularly difficult.
The study draws on data from the National Heart, Lung, and Blood Institute’s prospective national registry, the MDS Natural History Study. Of the 2,115 enrolled patients, 130 (6.1%) reported exposure to Agent Orange, and 96% of exposed patients were male. Ultimately, 54% of exposed patients received a diagnosis of MDS or a related prodromal condition compared with 37% of unexposed patients.
ASH’s preliminary findings showed that exposed veterans were younger and, on average, diagnosed approximately several years earlier than unexposed veterans. During the first two years after diagnosis, exposed patients were about 80% more likely to have worsening disease, including progression to more severe MDS or acute leukemia. However, overall survival was similar between the two groups throughout the study.
of Blood Advances The paper details the specific genetic changes behind that pattern. Researchers found that among patients diagnosed with MDS, those exposed to Agent Orange were more than twice as likely to have high-risk chromosomal abnormalities. These changes suggest that the disease acts aggressively.
Certain mutations such as TET2, SRSF2, U2AF1, ZRSR2, and KRAS appeared more frequently among exposed patients. Many of these changes affect how cells process genetic instructions and build proteins, a key step in keeping bone marrow cells healthy. When this process is interrupted, cells can grow abnormally and become cancerous.
“It’s not a single event that causes this cancer. You get one mutation, and then you get another. Over years or decades, those changes accumulate,” Sekeres said. “What we’re seeing is that Agent Orange has introduced mutations that will put patients on a path to cancer 50 years later.”
For veterans living with MDS, learning that their cancer may have a unique genetic profile provides more than scientific insight. It can influence subsequent care and treatment decisions. The high rate of early disease progression raises questions about long-term leukemia risk.
“If exposed veterans live long enough, we may also see a link between defoliants and leukemia,” Sekeres said.
The study revealed another notable pattern. Patients who reported exposure to Agent Orange in the registry were disproportionately black men compared to the demographics of the Vietnam military.
In the registry, about one in five exposed male patients is black, more than twice the rate among unexposed men. Even after adjusting for other factors, black veterans were nearly three times more likely to report exposure to Agent Orange.
“This number is disproportionate to the proportion of blacks who served in Vietnam,” Sekeres said. “Black people may have been more vulnerable during their military service and therefore more likely to be exposed to toxins like defoliants.”
Although this study was not designed to find out why, the findings highlight the need for further investigation into exposure patterns and long-term risks in specific groups.
After presenting his findings at the ASH conference, Sekeres said his inbox quickly filled up. Veterans from all over the country came together. Some had just been diagnosed. Others lived with MDS for years. Many wanted to know whether their illness was ultimately related to military service.
“There are older veterans with MDS who are being told by the veterans association that they cannot receive the medical coverage they need because there is no formal association,” Sekeres said.
This new analysis changes that dynamic. Although it does not prove cause and effect, it provides the strongest data to date linking exposure to Agent Orange to distinct genetic changes and a more aggressive disease. The data now exists for review by national review bodies.
“We hope that the Institute of Medicine will recognize that exposure to Agent Orange is a risk factor for MDS,” Professor Sekeres said. “We hope this publication will ultimately help ensure these veterans receive the service-connected care they deserve.”
sauce:
University of Miami Miller School of Medicine
Reference magazines:
Sekeres, Massachusetts others. (2026). Association between Agent Orange exposure and myelodysplastic syndrome. Blood Advances. DOI: 10.1182/bloodadvances.2025019262. https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2025019262/566835/Exposure-to-Agent-Orange-and-Association-with
