Research Answers Question Persisting for Decades
Mikkael Sekeres, MD, Professor of Medicine and the Chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center in Miami
MIAMI — For decades, questions have persisted about whether exposure to Agent Orange contributes to the development of blood cancers among Vietnam War veterans. New research sheds light on this issue, identifying a significant association between Agent Orange exposure and myelodysplastic syndromes (MDS), a group of bone marrow disorders that can progress to acute leukemia.
MDS is characterized by ineffective blood cell production, leading to cytopenias and, in some cases, progression to acute myeloid leukemia. The disease develops over time through the accumulation of genetic mutations, which may arise spontaneously or in response to environmental exposures. Among these, exposure to Agent Orange has been identified as a potential contributor to MDS risk.
Agent Orange, a herbicide widely used during the Vietnam War, has long been suspected as a potential contributor to cancer risk. Contaminated with dioxins—known carcinogens—it has been linked to several malignancies, but its role in MDS has remained uncertain.
“So I’ve been describing this as my passion project,” said Mikkael Sekeres, MD, Professor of Medicine and the Chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center in Miami.
“For years and years, I have been taking care of people who served in Vietnam who were exposed to Agent Orange and who developed myelodysplastic syndromes.”
Sekeres’ research, published in Blood Advances, draws on data from the National Heart, Lung, and Blood Institute’s MDS Natural History Study, a large prospective cohort that includes detailed clinical, genetic and exposure data from more than 2,000 patients. This dataset enabled an analysis that, for the first time, examined patients with confirmed MDS diagnoses alongside self-reported Agent Orange exposure, allowing for a more direct evaluation of the potential relationship.1
“There have not been any studies in the past … that have shown this connection,” Sekeres told U.S. Medicine, noting that previous efforts were limited by a lack of datasets that included both disease and exposure information.
Among 2,115 participants, 130 reported exposure to Agent Orange. These individuals were more likely to be diagnosed with MDS or related precursor conditions and tended to develop disease at a younger age than those without exposure.1
Despite the strength of the findings, Sekeres is careful to frame the results appropriately.
“Establishing causation is really hard,” he explained. “We don’t say that Agent Orange caused myelodysplastic syndrome. We say that Agent Orange exposure was associated with developing myelodysplastic syndrome.”
Still, he emphasized that the evidence is meaningful.
“This is about as good as you’re going to get for establishing a link between Agent Orange exposure and the development of myelodysplastic syndromes.”
One of the most compelling aspects of the study is its insight into the biological mechanisms that may underlie the association.
Exposure to Agent Orange, often occurring when servicemembers were in their late teens or early 20s, may introduce early genetic damage that sets the stage for disease decades later. According to Sekeres, cancer development typically requires multiple mutations over time.
“That very first exposure to Agent Orange … probably introduces the first mutation in that cell, and then a person has to live decades later to develop that second and the third and the fourth mutation before we actually get disease,” he said.
Consistent with this model, patients exposed to Agent Orange were found to have more genetic mutations overall, as well as higher rates of specific mutations and disrupted molecular pathways, particularly those involving RNA splicing and chromatin modification.
The findings also suggest that MDS in exposed individuals may be biologically distinct, with earlier onset and greater genetic complexity.
In addition to differences in disease onset and biology, the study found that patients exposed to Agent Orange experienced more rapid disease progression. Patients were more likely to transition from precursor conditions to MDS, or from lower-risk to higher-risk disease and acute leukemia, Sekeres said.
These findings also may have implications for how clinicians manage patients with a history of Agent Orange exposure. Sekeres suggested that earlier referral and closer monitoring may be warranted in this population, particularly when abnormalities in blood counts are identified. Given the potential for more rapid disease progression, a lower threshold for diagnostic evaluation—including bone marrow biopsy—could help identify MDS or its precursor conditions at an earlier stage.
Beyond clinical care, the findings may eventually have important policy implications.
“My hope is that this research will finally provide the data that the Veterans Administration feels is necessary to establish myelodysplastic syndrome as a risk from being exposed to Agent Orange and that these veterans will finally get the healthcare coverage that they deserve,” he said.
- Sekeres MA, DeZern AE, Otterstatter M, Padron E, et AL. Exposure to Agent Orange and Association with Myelodysplastic Syndromes. Blood Adv. 2026 Feb 24:bloodadvances.2025019262. doi: 10.1182/bloodadvances.2025019262. Epub ahead of print. PMID: 41734386.